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Fraenza F, Cagnotta C, Gaio M, Sportiello L, Scavone C, Capuano A, Trama U. Disproportionality analysis of European safety reports on autoimmune and rheumatic diseases following COVID-19 vaccination. Sci Rep 2025; 15:14740. [PMID: 40289148 PMCID: PMC12034749 DOI: 10.1038/s41598-025-98313-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Accepted: 04/10/2025] [Indexed: 04/30/2025] Open
Abstract
The safety profile of COVID-19 vaccines is well-established, yet the widespread immunization campaign has led to an increase in reported cases of Immune-Mediated and Rheumatic Diseases (IMDRs). This study aimed to assess the reporting of Adverse Events Following Immunization (AEFIs) related to IMDRs after COVID-19 vaccination. We analyzed all individual case safety reports (ICSRs) related to COVID-19 vaccines authorized in the European Union (i.e., tozinameran, elasomeran, ChAdOx1-S NCoV-19, and Ad26.Cov2.S) registered in the EudraVigilance (EV) database from January 1, 2021, to October 23, 2023. Our analysis identified ICSRs with events indicative of IMDRs and conducted disproportionality analysis (i.e., Reporting Odds Ratio (ROR) with 95% CI) to examine the frequency of different IMDR types linked to each vaccine. In total, 45,352 ICSRs reported at least one AEFI associated with rheumatic or autoimmune conditions, with 54% of them implicating tozinameran as the suspected vaccine. More than half of the reported AEFIs were classified as serious, with approximately 45% remaining unresolved. The most frequently reported conditions were other immune-mediated diseases, followed by arthritis, vasculitis, systemic lupus erythematosus, and tendinopathies. Our disproportionality analysis suggested that mRNA vaccines may be more frequently associated with new autoimmune rheumatic diseases. Stratified analysis revealed significant associations for ChAd, particularly in vasculitis and tendinopathies, only when compared to Ad26.Cov2.S. Real-world pharmacovigilance data suggest that autoimmune and rheumatic diseases may be under-reported following COVID-19 vaccination, highlighting the need for further research to better understand the underlying mechanisms. The findings from this disproportionality analysis suggest the need for further studies to investigate these results in greater depth.
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Affiliation(s)
- Federica Fraenza
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Naples, Italy
| | - Cecilia Cagnotta
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Naples, Italy
| | - Mario Gaio
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Naples, Italy.
- Department of Life Science, Health, and Health Professions, Link Campus University, Rome, Italy.
| | - Liberata Sportiello
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Naples, Italy
| | - Cristina Scavone
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Naples, Italy
| | - Annalisa Capuano
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Naples, Italy
| | - Ugo Trama
- Regional Pharmaceutical Unit, Campania Region, Naples, Italy
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Safi D, Khouri F, Zareef R, Arabi M. Antivirals in COVID-19: A Focus on Pediatric Cardiac Patients. THE CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY = JOURNAL CANADIEN DES MALADIES INFECTIEUSES ET DE LA MICROBIOLOGIE MEDICALE 2025; 2025:4573096. [PMID: 40196380 PMCID: PMC11972864 DOI: 10.1155/cjid/4573096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Accepted: 03/17/2025] [Indexed: 04/09/2025]
Abstract
The COVID-19 pandemic created an unprecedented public health crisis, driven by its rapid global spread and the urgent need for worldwide collaborative interventions to contain it. This urgency spurred the search for therapeutic agents to prevent or manage the infection. Among these, various types of antivirals emerged as a prominent treatment option, supported by a wealth of observational studies and randomized controlled trials. The results from such studies conflict, with some concluding efficacy and others the lack thereof, with variability also occurring depending on the severity of COVID-19 in the studied population. In addition, many agents have been explored using randomized controlled trials-the gold standard in evaluating the efficacy of an intervention-to only a limited degree, with most of the evidence behind their use concluded using observational studies. Thus, the sheer volume of data has made it challenging to resolve inconsistencies and determine true efficacy. Furthermore, there is a paucity in the literature regarding the use of antivirals in the pediatric population infected with COVID-19, with their use being extrapolated from the results of studies done on adult patients. As such, additional trials are needed to solidify the effectiveness of antivirals in managing COVID-19, particularly in the underexplored and especially vulnerable pediatric cardiac patients. Therefore, utilizing the results from randomized controlled trials, this narrative review evaluates the rationale behind the use of antivirals, summarizes the findings from the literature, and concludes with a focused discussion on their application in pediatric cardiac patients.
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Affiliation(s)
- Dalia Safi
- Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Farah Khouri
- Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Rana Zareef
- Department of Pediatric and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Mariam Arabi
- Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon
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Omotoso OD, Joshua FO, Oyebamiji AK, Ebenezer O. Molecular Modeling Studies of Similar Molecules to Selective Estrogen Receptor Degrader Elacestrant as Inhibitors of SARS-COV-2. Cell Biochem Biophys 2025; 83:741-753. [PMID: 39259409 DOI: 10.1007/s12013-024-01506-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/25/2024] [Indexed: 09/13/2024]
Abstract
Coronavirus 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) strain. Many anticancer compounds have been repurposed as effective anti-coronavirus agents and are currently in a clinical trial to be evaluated for treatment. Elacestrant is a novel selective estrogen receptor degrader (SERD). A fingerprint Tanimoto-based 2-dimensional similarity search was performed in the PubChem database using elacestrant as a prototype. The chemical compounds were downloaded, and virtual screening, molecular docking, and molecular dynamics were further used to identify the most active molecules in the binding pocket SARS-COV-2 main protease. Eight compounds with superior docking score, gscore, and glide binding energy were identified. Molecular dynamic simulations (MD) were performed at 100 ns to remove the false interactions between the receptor and the active ligands. The results showed that all the compounds displayed good stability. Further, the ADMET results showed that compounds CID58023104 was observed to be deemed a hit compound; hence, CID58023104 and could be optimize, derivatize, and explore for further development as an anti-coronavirus agent targeting SARS-COV-2 main protease.
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Affiliation(s)
- Oluwadamilare D Omotoso
- Department of Bioinformatics, Faculty of Chemistry, Wybrzeze Stanislawa Wyspianskiego,, Waclow University of Science and Technology, Wroclaw, Poland
| | - Funsho Oyetunde Joshua
- Center of excellence for pharmaceutical sciences Northwest University, Potchefstroom, South Africa
| | - Abel Kolawole Oyebamiji
- Department of Chemistry and Industrial Chemistry, Bowen University, Iwo, Osun State, Nigeria
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Darne P, Vidhate S, Shintre S, Wagdare S, Bhamare D, Mehta N, Rajagopalan V, Padmanabhan S. Advancements in Antiviral Therapy: Favipiravir Sodium in Nasal Formulation. AAPS PharmSciTech 2024; 25:273. [PMID: 39592539 DOI: 10.1208/s12249-024-02986-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Accepted: 10/29/2024] [Indexed: 11/28/2024] Open
Abstract
Favipiravir (FPV) is an Active Pharmaceutical Ingredient (API) known to have lower solubility in aqueous solvents. In the current study, efforts were made to generate a crystalline Favipiravir Sodium Salt (NaFPV) for enhanced solubility in aqueous media. The in-house generated NaFPV was characterized by NMR studies and its sodium content was determined by Flame Emission Spectroscopy (FES) as a confirmation of salt formation. Its solubility was determined where-in the solubility of NaFPV in water was about 100 times greater than FVP. FPV and NaFPV nasal spray formulations were prepared and its activity was determined against human coronavirus (hCoV) 229E strain. In the anti-hCoV assay as compared to FPV, NaFPV showed almost threefold higher anti-viral activity than its unmodified counterpart. Accelerated stability and spray pattern characteristics of both the formulations were studied. Interestingly, NaFPV showed higher physical stability during storage at conditions 40 ± 2 °C/ 75% ± 5% RH. The nasal spray formulations of both FPV and NaFPV showed ideal plume geometry and spray pattern of acceptable specifications. Due to its improvement in terms of solubility, NaFPV will have higher rate and extent of absorption, and faster onset of the therapeutic effect and may appear to be a feasible alternative to regular favipiravir for use in solid dosage forms.
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Affiliation(s)
- Priti Darne
- Innovation and Drug Discovery Division, Sava Healthcare Limited, Research Center, Block D1, Plot No. 17/6, MIDC, Chinchwad, Pune-411019, India
| | - Shankar Vidhate
- Innovation and Drug Discovery Division, Sava Healthcare Limited, Research Center, Block D1, Plot No. 17/6, MIDC, Chinchwad, Pune-411019, India
| | - Somesh Shintre
- Innovation and Drug Discovery Division, Sava Healthcare Limited, Research Center, Block D1, Plot No. 17/6, MIDC, Chinchwad, Pune-411019, India
| | - Somnath Wagdare
- Analytical Development Laboratory Division, Sava Healthcare Limited, Research Center, Block D1, Plot No. 17/6, MIDC, Chinchwad, Pune-411019, India
| | - Dhiraj Bhamare
- Analytical Development Laboratory Division, Sava Healthcare Limited, Research Center, Block D1, Plot No. 17/6, MIDC, Chinchwad, Pune-411019, India
| | - Nisha Mehta
- Innovation and Drug Discovery Division, Sava Healthcare Limited, Research Center, Block D1, Plot No. 17/6, MIDC, Chinchwad, Pune-411019, India
| | - Vishal Rajagopalan
- Innovation and Drug Discovery Division, Sava Healthcare Limited, Research Center, Block D1, Plot No. 17/6, MIDC, Chinchwad, Pune-411019, India
| | - Sriram Padmanabhan
- Innovation and Drug Discovery Division, Sava Healthcare Limited, Research Center, Block D1, Plot No. 17/6, MIDC, Chinchwad, Pune-411019, India.
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Vinutha M, Sharma UR, Swamy G, Rohini S, Vada S, Janandri S, Haribabu T, Taj N, Gayathri SV, Jyotsna SK, Mudagal MP. COVID-19-related liver injury: Mechanisms, diagnosis, management; its impact on pre-existing conditions, cancer and liver transplant: A comprehensive review. Life Sci 2024; 356:123022. [PMID: 39214285 DOI: 10.1016/j.lfs.2024.123022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 08/20/2024] [Accepted: 08/25/2024] [Indexed: 09/04/2024]
Abstract
AIMS This review explores the mechanisms, diagnostic approaches, and management strategies for COVID-19-induced liver injury, with a focus on its impact on patients with pre-existing liver conditions, liver cancer, and those undergoing liver transplantation. MATERIALS AND METHODS A comprehensive literature review included studies on clinical manifestations of liver injury due to COVID-19. Key areas examined were direct viral effects, drug-induced liver injury, cytokine storms, and impacts on individuals with chronic liver diseases, liver transplants, and the role of vaccination. Data were collected from clinical trials, observational studies, case reports, and review literature. KEY FINDINGS COVID-19 can cause a spectrum of liver injuries, from mild enzyme elevations to severe hepatic dysfunction. Injury mechanisms include direct viral invasion, immune response alterations, drug toxicity, and hypoxia-reperfusion injury. Patients with chronic liver conditions (such as alcohol-related liver disease, nonalcoholic fatty liver disease, cirrhosis, and hepatocellular carcinoma) face increased risks of severe outcomes. The pandemic has worsened pre-existing liver conditions, disrupted cancer treatments, and complicated liver transplantation. Vaccination remains crucial for reducing severe disease, particularly in chronic liver patients and transplant recipients. Telemedicine has been beneficial in managing patients and reducing cross-infection risks. SIGNIFICANCE This review discusses the importance of improved diagnostic methods and management strategies for liver injury caused by COVID-19. It emphasizes the need for close monitoring and customized treatment for high-risk groups, advocating for future research to explore long-term effects, novel therapies, and evidence-based approaches to improve liver health during and after the pandemic.
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Affiliation(s)
- M Vinutha
- Department of Pharmacology, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, India
| | - Uday Raj Sharma
- Department of Pharmacology, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, India.
| | - Gurubasvaraja Swamy
- Department of Pharmaceutical Chemistry, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, India
| | - S Rohini
- Department of Pharmacology, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, India
| | - Surendra Vada
- Department of Pharmacology, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, India
| | - Suresh Janandri
- Department of Pharmacology, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, India
| | - T Haribabu
- Department of Pharmacology, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, India
| | - Nageena Taj
- Department of Pharmacology, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, India
| | - S V Gayathri
- Department of Pharmacology, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, India
| | - S K Jyotsna
- Department of Pharmacology, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, India
| | - Manjunatha P Mudagal
- Department of Pharmacology, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, India
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Ciudad CJ, Valiuska S, Rojas JM, Nogales-Altozano P, Aviñó A, Eritja R, Chillón M, Sevilla N, Noé V. Polypurine reverse hoogsteen hairpins as a therapeutic tool for SARS-CoV-2 infection. J Biol Chem 2024; 300:107884. [PMID: 39395809 PMCID: PMC11570937 DOI: 10.1016/j.jbc.2024.107884] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 10/01/2024] [Accepted: 10/06/2024] [Indexed: 10/14/2024] Open
Abstract
Although the COVID-19 pandemic was declared no longer a global emergency by the World Health Organization in May 2023, SARS-CoV-2 is still infecting people across the world. Many therapeutic oligonucleotides such as ASOs, siRNAs, or CRISPR-based systems emerged as promising antiviral strategies for the treatment of SARS-CoV-2. In this work, we explored the inhibitory potential on SARS-CoV-2 replication of Polypurine Reverse Hoogsteen Hairpins (PPRHs), CC1-PPRH, and CC3-PPRH, targeting specific polypyrimidine sequences within the replicase and Spike regions, respectively, and previously validated for COVID-19 diagnosis. Both PPRHs are bound to their target sequences in the viral genome with high affinity in the order of nM. In vitro, both PPRHs reduced viral replication by more than 92% when transfected into VERO-E6 cells 24 h prior to infection with SARS-CoV-2. In vivo intranasal administration of CC1-PPRH in K18-hACE2 mice expressing the human ACE receptor protected all the animals from SARS-CoV-2 infection. The properties of PPRHs position them as promising candidates for the development of novel therapeutics against SARS-CoV-2 and other viral infections.
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Affiliation(s)
- Carlos J Ciudad
- Department of Biochemistry & Physiology, School Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain; Institut de Nanociencia i Nanotecnologia (IN2UB), Universitat de Barcelona, Barcelona, Spain.
| | - Simonas Valiuska
- Department of Biochemistry & Physiology, School Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain; Institut de Nanociencia i Nanotecnologia (IN2UB), Universitat de Barcelona, Barcelona, Spain
| | - José Manuel Rojas
- Centro de Investigación en Sanidad Animal-CISA, INIA, CSIC, Madrid, Spain
| | | | - Anna Aviñó
- Institute for Advanced Chemistry of Catalonia, CSIC, Barcelona, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, Madrid, Spain
| | - Ramón Eritja
- Institute for Advanced Chemistry of Catalonia, CSIC, Barcelona, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, Madrid, Spain
| | - Miguel Chillón
- Institute of Neurosciences, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Noemí Sevilla
- Centro de Investigación en Sanidad Animal-CISA, INIA, CSIC, Madrid, Spain
| | - Verónique Noé
- Department of Biochemistry & Physiology, School Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain; Institut de Nanociencia i Nanotecnologia (IN2UB), Universitat de Barcelona, Barcelona, Spain
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Chakraborty A, Ghosh R, Soumya Mohapatra S, Barik S, Biswas A, Chowdhuri S. Repurposing of antimycobacterium drugs for COVID-19 treatment by targeting SARS CoV-2 main protease: An in-silico perspective. Gene 2024; 922:148553. [PMID: 38734190 DOI: 10.1016/j.gene.2024.148553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 04/27/2024] [Accepted: 05/08/2024] [Indexed: 05/13/2024]
Abstract
The global mortality rate has been significantly impacted by the COVID-19 pandemic, caused by the SARS CoV-2 virus. Although the pursuit for a potent antiviral is still in progress, experimental therapies based on repurposing of existing drugs is being attempted. One important therapeutic target for COVID-19 is the main protease (Mpro) that cleaves the viral polyprotein in its replication process. Recently minocycline, an antimycobacterium drug, has been successfully implemented for the treatment of COVID-19 patients. But it's mode of action is still far from clear. Furthermore, it remains unresolved whether alternative antimycobacterium drugs can effectively regulate SARS CoV-2 by inhibiting the enzymatic activity of Mpro. To comprehend these facets, eight well-established antimycobacterium drugs were put through molecular docking experiments. Four of the antimycobacterium drugs (minocycline, rifampicin, clofazimine and ofloxacin) were selected by comparing their binding affinities towards Mpro. All of the four drugs interacted with both the catalytic residues of Mpro (His41 and Cys145). Additionally, molecular dynamics experiments demonstrated that the Mpro-minocyline complex has enhanced stability, experiences reduced conformational fluctuations and greater compactness than other three Mpro-antimycobacterium and Mpro-N3/lopinavir complexes. This research furnishes evidences for implementation of minocycline against SARS CoV-2. In addition, our findings also indicate other three antimycobacterium/antituberculosis drugs (rifampicin, clofazimine and ofloxacin) could potentially be evaluated for COVID-19 therapy.
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Affiliation(s)
- Ayon Chakraborty
- University Institute of Biotechnology, University Centre for Research & Development, Chandigarh University, Mohali, India
| | - Rajesh Ghosh
- School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Bhubaneswar, India
| | | | - Subhashree Barik
- School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Bhubaneswar, India
| | - Ashis Biswas
- School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Bhubaneswar, India.
| | - Snehasis Chowdhuri
- School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Bhubaneswar, India.
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Pourhoseingholi MA, Looha MA, Ilkhani S, Hatamabadi H, Sadeghi A, Safavi-Naini SAA, Heidari K, Taraghikhah N, Fallah MM, Kalantar R, Naderi N, Esbati R, Ebrahimi N, Solhpour A, Jamialahmadi T, Sahebkar A. Assessing the effect of remdesivir alone and in combination with corticosteroids on time to death in COVID-19: A propensity score-matched analysis. JOURNAL OF CLINICAL VIROLOGY PLUS 2024; 4:100180. [DOI: 10.1016/j.jcvp.2024.100180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2024] Open
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Zhang Z, Zheng H, Liu Y, Ma S, Feng Q, Qu J, Zhu X. Highly sensitive detection of multiple antiviral drugs using graphitized hydroxylated multi-walled carbon nanotubes/ionic liquids-based electrochemical sensors. ENVIRONMENTAL RESEARCH 2024; 249:118466. [PMID: 38354882 DOI: 10.1016/j.envres.2024.118466] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 02/06/2024] [Accepted: 02/10/2024] [Indexed: 02/16/2024]
Abstract
Global outbreaks and the spread of viral diseases in the recent years have led to a rapid increase in the usage of antiviral drugs (ATVs), the residues and metabolites of which are discharged into the natural environment, posing a serious threat to human health. There is an urgent need to develop sensitive and rapid detection tools for multiple ATVs. In this study, we developed a highly sensitive electrochemical sensor comprising a glassy carbon electrode (GCE) modified with graphitized hydroxylated multi-walled carbon nanotubes (G-MWCNT-OH) and 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6, IL) for the detection of six ATVs including famciclovir (FCV), remdesivir (REM), favipiravir (FAV), hydroxychloroquine sulfate (HCQ), cepharanthine (CEP) and molnupiravir (MOL). The morphology and structure of the G-MWCNT-OH/IL nanocomposites were characterized comprehensively, and the electroactive surface area and electron conductivity of G-MWCNT-OH/IL/GCE were determined using cyclic voltammetry and electrochemical impedance spectroscopy. The thermodynamic stability and non-covalent interactions between the G-MWCNT-OH and IL were evaluated through quantum chemical simulation calculations, and the mechanism of ATV detection using the G-MWCNT-OH/IL/GCE was thoroughly examined. The detection conditions were optimized to improve the sensitivity and stability of electrochemical sensors. Under the optimal experimental conditions, the G-MWCNT-OH/IL/GCE exhibited excellent electrocatalytic performance and detected the ATVs over a wide concentration range (0.01-120 μM). The limit of detections (LODs) were 42.3 nM, 55.4 nM, 21.9 nM, 15.6 nM, 10.6 nM, and 3.2 nM for FCV, REM, FAV, HCQ, CEP, and MOL, respectively. G-MWCNT-OH/IL/GCE was also highly stable and selective to the ATVs in the presence of multiple interfering analytes. This sensor exhibited great potential for enabling the quantitative detection of multiple ATVs in actual water environment.
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Affiliation(s)
- Zhipeng Zhang
- School of Environment, Northeast Normal University, Changchun, 130117, PR China
| | - Huizi Zheng
- School of Environment, Northeast Normal University, Changchun, 130117, PR China
| | - Ying Liu
- School of Environment, Northeast Normal University, Changchun, 130117, PR China
| | - Shuang Ma
- School of Environment, Northeast Normal University, Changchun, 130117, PR China
| | - Qi Feng
- School of Environment, Northeast Normal University, Changchun, 130117, PR China
| | - Jiao Qu
- School of Environment, Northeast Normal University, Changchun, 130117, PR China
| | - Xiaolin Zhu
- School of Environment, Northeast Normal University, Changchun, 130117, PR China.
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Ul Mustafa Z, Batool A, Ibrar H, Salman M, Khan YH, Mallhi TH, Meyer JC, Godman B, Moore CE. Bacterial co-infections, secondary infections and antimicrobial use among hospitalized COVID-19 patients in the sixth wave in Pakistan: findings and implications. Expert Rev Anti Infect Ther 2024; 22:229-240. [PMID: 38146949 DOI: 10.1080/14787210.2023.2299387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 11/15/2023] [Indexed: 12/27/2023]
Abstract
INTRODUCTION Previous studies in Pakistan have shown considerable over prescribing of antibiotics in patients hospitalized with COVID-19 despite very low prevalence of bacterial infections. Irrational use of antibiotics will worsen antimicrobial resistance (AMR). METHODS Retrospective analysis of medical records of patients in the COVID-19 wards of three tertiary care hospitals to assess antibiotic use during the sixth COVID-19 wave. RESULTS A total of 284 patients were included, most were male (66.9%), aged 30-50 years (50.7%) with diabetes mellitus the most common comorbidity. The most common symptoms at presentation were cough (47.9%) and arthralgia-myalgia (41.5%). Around 3% were asymptomatic, 34.9% had mild, 30.3% moderate, and 23.6% had severe disease, with 8.1% critical. Chest X-ray abnormalities were seen in 43.3% of patients and 37% had elevated white cell counts, with 35.2% having elevated C-reactive protein levels. Around 91% COVID-19 patients were prescribed antibiotics during their hospital stay, with only a few with proven bacterial co-infections or secondary bacterial infections. Most antibiotics were from the 'Watch' category (90.8%) followed by the 'Reserve' category (4.8%), similar to previous COVID-19 waves. CONCLUSION There continued to be excessive antibiotics use among hospitalized COVID-19 patients in Pakistan. Urgent measures are needed to address inappropriate prescribing including greater prescribing of Access antibiotics where pertinent.
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Affiliation(s)
- Zia Ul Mustafa
- Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia
- Department of Pharmacy Services, District Headquarter (DHQ) Hospital, Pakpattan, Pakistan
| | - Arfa Batool
- Department of Medicine, Sheikh Zaid Medical College, Rahim Yar Khan, Pakistan
| | - Hadia Ibrar
- Department of Medicine, Wah Medical College, Rawalpindi, Pakistan
| | - Muhammad Salman
- Institute of Pharmacy, Faculty of Pharmaceutical and Allied Health Sciences, Lahore College for Women University, Lahore, Pakistan
| | - Yusra Habib Khan
- Department of Clinical Pharmacy, College of Pharmacy, Jouf University, Sakaka, Saudi Arabia
| | - Tauqeer Hussain Mallhi
- Department of Clinical Pharmacy, College of Pharmacy, Jouf University, Sakaka, Saudi Arabia
| | - Johanna C Meyer
- Department of Public Health Pharmacy and Management, School of Pharmacy, Sefako Makgatho Health Sciences University, Ga-Rankuwa, South Africa
- South African Vaccination and Immunisation Centre, Sefako Makgatho Health Sciences University, Garankuwa, Pretoria, South Africa
| | - Brian Godman
- Department of Public Health Pharmacy and Management, School of Pharmacy, Sefako Makgatho Health Sciences University, Ga-Rankuwa, South Africa
- Strathclyde Institute of Pharmacy and Biomedical Science (SIPBS), University of Strathclyde, Glasgow, UK
| | - Catrin E Moore
- Centre for Neonatal and Pediatric Infection, St. George's University of London, London, UK
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11
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Wang Y, Yang Z, Yao Q. Accurate and interpretable drug-drug interaction prediction enabled by knowledge subgraph learning. COMMUNICATIONS MEDICINE 2024; 4:59. [PMID: 38548835 PMCID: PMC10978847 DOI: 10.1038/s43856-024-00486-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Accepted: 03/18/2024] [Indexed: 04/01/2024] Open
Abstract
BACKGROUND Discovering potential drug-drug interactions (DDIs) is a long-standing challenge in clinical treatments and drug developments. Recently, deep learning techniques have been developed for DDI prediction. However, they generally require a huge number of samples, while known DDIs are rare. METHODS In this work, we present KnowDDI, a graph neural network-based method that addresses the above challenge. KnowDDI enhances drug representations by adaptively leveraging rich neighborhood information from large biomedical knowledge graphs. Then, it learns a knowledge subgraph for each drug-pair to interpret the predicted DDI, where each of the edges is associated with a connection strength indicating the importance of a known DDI or resembling strength between a drug-pair whose connection is unknown. Thus, the lack of DDIs is implicitly compensated by the enriched drug representations and propagated drug similarities. RESULTS Here we show the evaluation results of KnowDDI on two benchmark DDI datasets. Results show that KnowDDI obtains the state-of-the-art prediction performance with better interpretability. We also find that KnowDDI suffers less than existing works given a sparser knowledge graph. This indicates that the propagated drug similarities play a more important role in compensating for the lack of DDIs when the drug representations are less enriched. CONCLUSIONS KnowDDI nicely combines the efficiency of deep learning techniques and the rich prior knowledge in biomedical knowledge graphs. As an original open-source tool, KnowDDI can help detect possible interactions in a broad range of relevant interaction prediction tasks, such as protein-protein interactions, drug-target interactions and disease-gene interactions, eventually promoting the development of biomedicine and healthcare.
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Affiliation(s)
| | - Zaifei Yang
- Baidu Research, Baidu Inc., Beijing, China
- Institute of Computing Technology, Chinese Academy of Sciences, Beijing, China
| | - Quanming Yao
- Department of Electronic Engineering, Tsinghua University, Beijing, China.
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12
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Purrmann L, Speichert LJ, Bäuerle A, Teufel M, Krakowczyk JB, Beckord J, Felderhoff-Müser U, Skoda EM, Dinse H. COVID-19 Vaccine for Children: Determinants and Beliefs Contributing to Vaccination Decision of Parents in Germany 2021/2022. Vaccines (Basel) 2023; 12:20. [PMID: 38250833 PMCID: PMC10820980 DOI: 10.3390/vaccines12010020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Revised: 12/13/2023] [Accepted: 12/15/2023] [Indexed: 01/23/2024] Open
Abstract
To reduce the number of COVID-19 cases, vaccines were rapidly made available worldwide. For a strategically targeted response to the COVID-19 pandemic, population vaccination coverage was to be maximized. The target groups also included healthy children. In this context, it is important to understand the determinants and beliefs that lead parents to favor or oppose COVID-19 immunization in children. This study aimed to investigate parents' COVID-19 vaccination willingness in Germany for children aged 5-11 years in 2021/2022. For this purpose, the determinants and beliefs behind parents' vaccination decisions were examined. Descriptive analysis and bivariate correlations were performed on COVID-19 vaccination willingness and parents' mental health status, general vaccination attitudes, and SARS-CoV-2 politics perceptions. In total, 2401 participants fully participated in this cross-sectional study. The COVID-19 vaccination uptake (71.4%) outweighed the vaccination refusal (19.4%). Correlations revealed higher vaccine acceptance in parents presenting full vaccination certificates (90.9%), COVID-19 immunizations (99.9%), or increased COVID-19 fear (93.6%). Vaccination-refusal was associated with higher perceived pressure by COVID-19 vaccination campaigns (87.7%), higher experienced restrictions due to COVID-19 protective measures in parents' social environment (83.6%), and engagement against COVID-19 protective measures (51.6%). Besides general anxiety, no significant correlations were observed between parents' mental health variables and vaccination willingness. Although several factors are ultimately associated with vaccination willingness, future vaccination campaigns should prioritize reducing pressure, increasing trust, and considering parents' differentiation between familiar and unfamiliar pathogens during their vaccination decision-making process.
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Affiliation(s)
- Laura Purrmann
- Clinic for Psychosomatic Medicine and Psychotherapy, LVR-University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
| | - Leoni-Johanna Speichert
- Clinic for Psychosomatic Medicine and Psychotherapy, LVR-University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
| | - Alexander Bäuerle
- Clinic for Psychosomatic Medicine and Psychotherapy, LVR-University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
- Centre for Translational Neuro- and Behavioral Sciences (C-TNBS), University of Duisburg-Essen, 45147 Essen, Germany
| | - Martin Teufel
- Clinic for Psychosomatic Medicine and Psychotherapy, LVR-University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
- Centre for Translational Neuro- and Behavioral Sciences (C-TNBS), University of Duisburg-Essen, 45147 Essen, Germany
| | - Julia Barbara Krakowczyk
- Clinic for Psychosomatic Medicine and Psychotherapy, LVR-University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
- Centre for Translational Neuro- and Behavioral Sciences (C-TNBS), University of Duisburg-Essen, 45147 Essen, Germany
| | - Jil Beckord
- Clinic for Psychosomatic Medicine and Psychotherapy, LVR-University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
- Centre for Translational Neuro- and Behavioral Sciences (C-TNBS), University of Duisburg-Essen, 45147 Essen, Germany
| | - Ursula Felderhoff-Müser
- Department of Pediatrics I, University Hospital of Essen, University of Duisburg-Essen, 45147 Essen, Germany
| | - Eva-Maria Skoda
- Clinic for Psychosomatic Medicine and Psychotherapy, LVR-University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
- Centre for Translational Neuro- and Behavioral Sciences (C-TNBS), University of Duisburg-Essen, 45147 Essen, Germany
| | - Hannah Dinse
- Clinic for Psychosomatic Medicine and Psychotherapy, LVR-University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
- Centre for Translational Neuro- and Behavioral Sciences (C-TNBS), University of Duisburg-Essen, 45147 Essen, Germany
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13
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Jash R, Prasanth DSNBK, Jash M, Suneetha A. Small molecules in the race of COVID-19 drug development. JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH 2023; 25:1133-1154. [PMID: 37066495 DOI: 10.1080/10286020.2023.2197595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 03/28/2023] [Accepted: 03/28/2023] [Indexed: 06/19/2023]
Abstract
COVID-19, caused by SARS-CoV-2, is spreading worldwide, regardless of different continents, increasing the death toll to almost five million, with more than 300 million reported cases. Researchers have been fighting the greatest threats to human civilization. This report provides a glimpse of ongoing small-molecule research on COVID-19 drugs to save millions of lives, which may provide researchers with a better understanding of rigorously investigated therapeutic agents. This report emphasizes the chemical structures and mechanisms of activity along with drug target information for several small molecules, including marketable drugs and agents under investigation.
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Affiliation(s)
- Rajiv Jash
- Department of Pharmacy, Sanaka Educational Trust Group of Institutions, Durgapur, West Bengal 713 212, India
| | - D S N B K Prasanth
- Department of Pharmacognosy, KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada, Andhra Pradesh 520 010, India
| | - Moumita Jash
- Department of Pharmacy, Sanaka Educational Trust Group of Institutions, Durgapur, West Bengal 713 212, India
- Department of Bioscience and Bioengineering, Indian Institute of Technology, Jodhpur, Rajasthan 342037, India
| | - Achanti Suneetha
- Department of Pharmaceutical Analysis, KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada, Andhra Pradesh 520 010, India
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14
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Yevsieieva LV, Lohachova KO, Kyrychenko A, Kovalenko SM, Ivanov VV, Kalugin ON. Main and papain-like proteases as prospective targets for pharmacological treatment of coronavirus SARS-CoV-2. RSC Adv 2023; 13:35500-35524. [PMID: 38077980 PMCID: PMC10698513 DOI: 10.1039/d3ra06479d] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Accepted: 11/23/2023] [Indexed: 10/16/2024] Open
Abstract
The pandemic caused by the coronavirus SARS-CoV-2 led to a global crisis in the world healthcare system. Despite some progress in the creation of antiviral vaccines and mass vaccination of the population, the number of patients continues to grow because of the spread of new SARS-CoV-2 mutations. There is an urgent need for direct-acting drugs capable of suppressing or stopping the main mechanisms of reproduction of the coronavirus SARS-CoV-2. Several studies have shown that the successful replication of the virus in the cell requires proteolytic cleavage of the protein structures of the virus. Two proteases are crucial in replicating SARS-CoV-2 and other coronaviruses: the main protease (Mpro) and the papain-like protease (PLpro). In this review, we summarize the essential viral proteins of SARS-CoV-2 required for its viral life cycle as targets for chemotherapy of coronavirus infection and provide a critical summary of the development of drugs against COVID-19 from the drug repurposing strategy up to the molecular design of novel covalent and non-covalent agents capable of inhibiting virus replication. We overview the main antiviral strategy and the choice of SARS-CoV-2 Mpro and PLpro proteases as promising targets for pharmacological impact on the coronavirus life cycle.
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Affiliation(s)
- Larysa V Yevsieieva
- School of Chemistry, V. N. Karazin Kharkiv National University 4 Svobody sq. Kharkiv 61022 Ukraine
| | - Kateryna O Lohachova
- School of Chemistry, V. N. Karazin Kharkiv National University 4 Svobody sq. Kharkiv 61022 Ukraine
| | - Alexander Kyrychenko
- School of Chemistry, V. N. Karazin Kharkiv National University 4 Svobody sq. Kharkiv 61022 Ukraine
| | - Sergiy M Kovalenko
- School of Chemistry, V. N. Karazin Kharkiv National University 4 Svobody sq. Kharkiv 61022 Ukraine
| | - Volodymyr V Ivanov
- School of Chemistry, V. N. Karazin Kharkiv National University 4 Svobody sq. Kharkiv 61022 Ukraine
| | - Oleg N Kalugin
- School of Chemistry, V. N. Karazin Kharkiv National University 4 Svobody sq. Kharkiv 61022 Ukraine
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15
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Gonzaga A, Andreu E, Hernández-Blasco LM, Meseguer R, Al-Akioui-Sanz K, Soria-Juan B, Sanjuan-Gimenez JC, Ferreras C, Tejedo JR, Lopez-Lluch G, Goterris R, Maciá L, Sempere-Ortells JM, Hmadcha A, Borobia A, Vicario JL, Bonora A, Aguilar-Gallardo C, Poveda JL, Arbona C, Alenda C, Tarín F, Marco FM, Merino E, Jaime F, Ferreres J, Figueira JC, Cañada-Illana C, Querol S, Guerreiro M, Eguizabal C, Martín-Quirós A, Robles-Marhuenda Á, Pérez-Martínez A, Solano C, Soria B. Rationale for combined therapies in severe-to-critical COVID-19 patients. Front Immunol 2023; 14:1232472. [PMID: 37767093 PMCID: PMC10520558 DOI: 10.3389/fimmu.2023.1232472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 08/22/2023] [Indexed: 09/29/2023] Open
Abstract
An unprecedented global social and economic impact as well as a significant number of fatalities have been brought on by the coronavirus disease 2019 (COVID-19), produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Acute SARS-CoV-2 infection can, in certain situations, cause immunological abnormalities, leading to an anomalous innate and adaptive immune response. While most patients only experience mild symptoms and recover without the need for mechanical ventilation, a substantial percentage of those who are affected develop severe respiratory illness, which can be fatal. The absence of effective therapies when disease progresses to a very severe condition coupled with the incomplete understanding of COVID-19's pathogenesis triggers the need to develop innovative therapeutic approaches for patients at high risk of mortality. As a result, we investigate the potential contribution of promising combinatorial cell therapy to prevent death in critical patients.
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Affiliation(s)
- Aitor Gonzaga
- Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain
- Institute of Bioengineering, Miguel Hernández University, Elche, Spain
| | - Etelvina Andreu
- Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain
- Applied Physics Department, Miguel Hernández University, Elche, Spain
| | | | - Rut Meseguer
- Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain
- Clinic University Hospital, Fundación para la Investigación del Hospital Clínico de la Comunidad Valenciana (INCLIVA) Health Research Institute, Valencia, Spain
| | - Karima Al-Akioui-Sanz
- Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain
- Hospital La Paz Institute for Health Research, IdiPAZ, University Hospital La Paz, Madrid, Spain
| | - Bárbara Soria-Juan
- Réseau Hospitalier Neuchâtelois, Hôpital Pourtalès, Neuchâtel, Switzerland
| | | | - Cristina Ferreras
- Hospital La Paz Institute for Health Research, IdiPAZ, University Hospital La Paz, Madrid, Spain
| | - Juan R. Tejedo
- Department of Molecular Biology and Biochemical Engineering, University Pablo de Olavide, Seville, Spain
- Biomedical Research Network for Diabetes and Related Metabolic Diseases-Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) of the Carlos III Health Institute (ISCIII), Madrid, Spain
| | - Guillermo Lopez-Lluch
- University Pablo de Olavide, Centro Andaluz de Biología del Desarrollo - Consejo Superior de Investigaciones Científicas (CABD-CSIC), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Sevilla, Spain
| | - Rosa Goterris
- Clinic University Hospital, Fundación para la Investigación del Hospital Clínico de la Comunidad Valenciana (INCLIVA) Health Research Institute, Valencia, Spain
| | - Loreto Maciá
- Nursing Department, University of Alicante, Alicante, Spain
| | - Jose M. Sempere-Ortells
- Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain
- Biotechnology Department, University of Alicante, Alicante, Spain
| | - Abdelkrim Hmadcha
- Department of Molecular Biology and Biochemical Engineering, University Pablo de Olavide, Seville, Spain
- Biosanitary Research Institute (IIB-VIU), Valencian International University (VIU), Valencia, Spain
| | - Alberto Borobia
- Clinical Pharmacology Department, La Paz University Hospital, School of Medicine, Universidad Autónoma de Madrid, IdiPAz, Madrid, Spain
| | - Jose L. Vicario
- Transfusion Center of the Autonomous Community of Madrid, Madrid, Spain
| | - Ana Bonora
- Health Research Institute Hospital La Fe, Valencia, Spain
| | | | - Jose L. Poveda
- Health Research Institute Hospital La Fe, Valencia, Spain
| | - Cristina Arbona
- Valencian Community Blood Transfusion Center, Valencia, Spain
| | - Cristina Alenda
- Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain
| | - Fabian Tarín
- Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain
| | - Francisco M. Marco
- Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain
- Immunology Department, Dr. Balmis General University Hospital, Alicante, Spain
| | - Esperanza Merino
- Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain
- Department of Clinical Medicine, Miguel Hernández University, Elche, Spain
- Infectious Diseases Unit, Dr. Balmis General University Hospital, Alicante, Spain
| | - Francisco Jaime
- Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain
| | - José Ferreres
- Intensive Care Service, Hospital Clinico Universitario, Fundación para la Investigación del Hospital Clínico de la Comunidad Valenciana (INCLIVA), Valencia, Spain
| | | | | | | | - Manuel Guerreiro
- Department of Hematology, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - Cristina Eguizabal
- Research Unit, Basque Center for Blood Transfusion and Human Tissues, Galdakao, Spain
- Cell Therapy, Stem Cells and Tissues Group, Biocruces Bizkaia Health Research Institute, Barakaldo, Spain
| | | | | | - Antonio Pérez-Martínez
- Hospital La Paz Institute for Health Research, IdiPAZ, University Hospital La Paz, Madrid, Spain
- Department of Pediatrics, Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain
| | - Carlos Solano
- Hematology Service, Hospital Clínico Universitario, Fundación para la Investigación del Hospital Clínico de la Comunidad Valenciana (INCLIVA), Valencia, Spain
| | - Bernat Soria
- Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain
- Institute of Bioengineering, Miguel Hernández University, Elche, Spain
- Biomedical Research Network for Diabetes and Related Metabolic Diseases-Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) of the Carlos III Health Institute (ISCIII), Madrid, Spain
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16
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Gudima G, Kofiadi I, Shilovskiy I, Kudlay D, Khaitov M. Antiviral Therapy of COVID-19. Int J Mol Sci 2023; 24:ijms24108867. [PMID: 37240213 DOI: 10.3390/ijms24108867] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 04/19/2023] [Accepted: 04/19/2023] [Indexed: 05/28/2023] Open
Abstract
Since the beginning of the COVID-19 pandemic, the scientific community has focused on prophylactic vaccine development. In parallel, the experience of the pharmacotherapy of this disease has increased. Due to the declining protective capacity of vaccines against new strains, as well as increased knowledge about the structure and biology of the pathogen, control of the disease has shifted to the focus of antiviral drug development over the past year. Clinical data on safety and efficacy of antivirals acting at various stages of the virus life cycle has been published. In this review, we summarize mechanisms and clinical efficacy of antiviral therapy of COVID-19 with drugs based on plasma of convalescents, monoclonal antibodies, interferons, fusion inhibitors, nucleoside analogs, and protease inhibitors. The current status of the drugs described is also summarized in relation to the official clinical guidelines for the treatment of COVID-19. In addition, here we describe innovative drugs whose antiviral effect is provided by antisense oligonucleotides targeting the SARS-CoV-2 genome. Analysis of laboratory and clinical data suggests that current antivirals successfully combat broad spectra of emerging strains of SARS-CoV-2 providing reliable defense against COVID-19.
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Affiliation(s)
- Georgii Gudima
- NRC Institute of Immunology, Federal Medico-Biological Agency, 115522 Moscow, Russia
| | - Ilya Kofiadi
- NRC Institute of Immunology, Federal Medico-Biological Agency, 115522 Moscow, Russia
- Department of Immunology, N.I. Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, 117997 Moscow, Russia
| | - Igor Shilovskiy
- NRC Institute of Immunology, Federal Medico-Biological Agency, 115522 Moscow, Russia
| | - Dmitry Kudlay
- NRC Institute of Immunology, Federal Medico-Biological Agency, 115522 Moscow, Russia
- Department of Pharmacology, Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia
| | - Musa Khaitov
- NRC Institute of Immunology, Federal Medico-Biological Agency, 115522 Moscow, Russia
- Department of Immunology, N.I. Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, 117997 Moscow, Russia
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17
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Laref S, Harrou F, Wang B, Sun Y, Laref A, Laleg-Kirati TM, Gojobori T, Gao X. Synergy of Small Antiviral Molecules on a Black-Phosphorus Nanocarrier: Machine Learning and Quantum Chemical Simulation Insights. Molecules 2023; 28:molecules28083521. [PMID: 37110754 PMCID: PMC10142408 DOI: 10.3390/molecules28083521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 04/03/2023] [Accepted: 04/10/2023] [Indexed: 04/29/2023] Open
Abstract
Favipiravir (FP) and Ebselen (EB) belong to a broad range of antiviral drugs that have shown active potential as medications against many viruses. Employing molecular dynamics simulations and machine learning (ML) combined with van der Waals density functional theory, we have uncovered the binding characteristics of these two antiviral drugs on a phosphorene nanocarrier. Herein, by using four different machine learning models (i.e., Bagged Trees, Gaussian Process Regression (GPR), Support Vector Regression (SVR), and Regression Trees (RT)), the Hamiltonian and the interaction energy of antiviral molecules in a phosphorene monolayer are trained in an appropriate way. However, training efficient and accurate models for approximating the density functional theory (DFT) is the final step in using ML to aid in the design of new drugs. To improve the prediction accuracy, the Bayesian optimization approach has been employed to optimize the GPR, SVR, RT, and BT models. Results revealed that the GPR model obtained superior prediction performance with an R2 of 0.9649, indicating that it can explain 96.49% of the data's variability. Then, by means of DFT calculations, we examine the interaction characteristics and thermodynamic properties in a vacuum and a continuum solvent interface. These results illustrate that the hybrid drug is an enabled, functionalized 2D complex with vigorous thermostability. The change in Gibbs free energy at different surface charges and temperatures implies that the FP and EB molecules are allowed to adsorb from the gas phase onto the 2D monolayer at different pH conditions and high temperatures. The results reveal a valuable antiviral drug therapy loaded by 2D biomaterials that may possibly open a new way of auto-treating different diseases, such as SARS-CoV, in primary terms.
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Affiliation(s)
- Slimane Laref
- Computational Bioscience Research Center (CBRC), King Abdullah University of Science & Technology (KAUST), Thuwal 23955-6900, Saudi Arabia
| | - Fouzi Harrou
- A Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia
| | - Bin Wang
- Center for Interfacial Reaction Engineering (CIRE), School of Chemical, Biological and Materials Engineering, University of Oklahoma, Norman, OK 73019, USA
| | - Ying Sun
- A Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia
| | - Amel Laref
- Department of Physics and Astronomy, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
| | - Taous-Meriem Laleg-Kirati
- A Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia
| | - Takashi Gojobori
- Computational Bioscience Research Center (CBRC), King Abdullah University of Science & Technology (KAUST), Thuwal 23955-6900, Saudi Arabia
| | - Xin Gao
- Computational Bioscience Research Center (CBRC), King Abdullah University of Science & Technology (KAUST), Thuwal 23955-6900, Saudi Arabia
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18
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Th-1, Th-2, Th-9, Th-17, Th-22 type cytokine concentrations of critical COVID-19 patients after treatment with Remdesivir. Immunobiology 2023; 228:152378. [PMID: 37058846 PMCID: PMC10036294 DOI: 10.1016/j.imbio.2023.152378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 02/22/2023] [Accepted: 03/20/2023] [Indexed: 03/26/2023]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread around the world causing a pandemic known as coronavirus disease 2019 (COVID-19). Cytokine storm was directly correlated with severity of COVID-19 syndromes. We evaluated the levels of 13 cytokines in ICU hospitalized COVID-19 patients (n=29) before, and after treatment with Remdesivir as well as in healthy controls (n=29). Blood samples were obtained from ICU patients during ICU admission (before treatment) and 5 days after treatment with Remdesivir. A group of 29 age- and gender-matched healthy controls was also studied. Cytokine levels were evaluated by multiplex immunoassay method using a fluorescence labeled cytokine panel. In comparison to cytokine levels measured at ICU admission, serum levels were reduced of IL-6 (134.75 pg/mL vs. 20.73 pg/mL, P< 0.0001), TNF-α (121.67 pg/mL vs. 10.15 pg/mL, P< 0.0001) and IFN-γ (29.69 pg/mL vs. 22.27 pg/mL, P= 0.005), whereas serum level was increased of IL-4 (8.47 pg/mL vs. 12.44 pg/mL, P= 0.002) within 5 days after Remdesivir treatment. Comparing with before treatment, Remdesivir significantly reduced the levels of inflammatory (258.98 pg/mL vs. 37.43 pg/mL, P< 0.0001), Th1-type (31.24 pg/mL vs. 24.46 pg/mL, P= 0.007), and Th17-type (36.79 pg/mL vs. 26.22 pg/mL, P< 0.0001) cytokines in critical COVID-19 patients. However, after Remdesivir treatment, the concentrations of Th2-type cytokines were significantly higher than before treatment (52.69 pg/mL vs. 37.09 pg/mL, P< 0.0001). In conclusion, Remdesivir led to decrease levels of Th1-type and Th17-type cytokines and increase Th2-type cytokines in critical COVID-19 patients 5 days after treatment.
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19
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Hassan H, Chiavaralli J, Hassan A, Bedda L, Krischuns T, Chen KY, Li ASM, Delpal A, Decroly E, Vedadi M, Naffakh N, Agou F, Mallart S, Arafa RK, Arimondo PB. Design and synthesis of naturally-inspired SARS-CoV-2 inhibitors. RSC Med Chem 2023; 14:507-519. [PMID: 36970153 PMCID: PMC10034039 DOI: 10.1039/d2md00149g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Accepted: 01/13/2023] [Indexed: 01/26/2023] Open
Abstract
A naturally inspired chemical library of 25 molecules was synthesised guided by 3-D dimensionality and natural product likeness factors to explore a new chemical space. The synthesised chemical library, consisting of fused-bridged dodecahydro-2a,6-epoxyazepino[3,4,5-c,d]indole skeletons, followed lead likeness factors in terms of molecular weight, C-sp3 fraction and Clog P. Screening of the 25 compounds against lung cells infected with SARS-CoV-2 led to the identification of 2 hits. Although the chemical library showed cytotoxicity, the two hits (3b, 9e) showed the highest antiviral activity (EC50 values of 3.7 and 1.4 μM, respectively) with an acceptable cytotoxicity difference. Computational analysis based on docking and molecular dynamics simulations against main protein targets in SARS-CoV-2 (main protease Mpro, nucleocapsid phosphoprotein, non-structural protein nsp10-nsp16 complex and RBD/ACE2 complex) were performed. The computational analysis proposed the possible binding targets to be either Mpro or the nsp10-nsp16 complex. Biological assays were performed to confirm this proposition. A cell-based assay for Mpro protease activity using a reverse-nanoluciferase (Rev-Nluc) reporter confirmed that 3b targets Mpro. These results open the way towards further hit-to-lead optimisations.
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Affiliation(s)
- Haitham Hassan
- Institut Pasteur, Department of Structural Biology and Chemistry, CNRS UMR no 3523 Chem4Life, Epigenetic Chemical Biology, Université Paris Cité F-75015 Paris France
| | - Jeanne Chiavaralli
- Institut Pasteur, Center for Technological Resources and Research (C2RT), CNRS UMR no 3523 Chem4Life, Chemogenomic and Biological Screening platform, Université Paris Cité F-75015 Paris France
| | - Afnan Hassan
- Drug Design and Discovery Lab, Zewail City of Science and Technology 12578 Cairo Egypt
- Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology 12578 Cairo Egypt
| | - Loay Bedda
- Drug Design and Discovery Lab, Zewail City of Science and Technology 12578 Cairo Egypt
- Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology 12578 Cairo Egypt
| | - Tim Krischuns
- Institut Pasteur, Unité Biologie des ARN et Virus Influenza, CNRS UMR3569, Université Paris Cité F-75015 Paris France
| | - Kuang-Yu Chen
- Institut Pasteur, Unité Biologie des ARN et Virus Influenza, CNRS UMR3569, Université Paris Cité F-75015 Paris France
| | - Alice Shi Ming Li
- Department of Pharmacology and Toxicology, University of Toronto Canada
| | - Adrien Delpal
- CNRS - UMR7257 - AFMB - Aix-Marseille Université Marseille France
| | - Etienne Decroly
- CNRS - UMR7257 - AFMB - Aix-Marseille Université Marseille France
| | - Masoud Vedadi
- Department of Pharmacology and Toxicology, University of Toronto Canada
- QBI COVID-19 Research Group (QCRG) San Francisco CA USA
| | - Nadia Naffakh
- Institut Pasteur, Unité Biologie des ARN et Virus Influenza, CNRS UMR3569, Université Paris Cité F-75015 Paris France
| | - Fabrice Agou
- Institut Pasteur, Center for Technological Resources and Research (C2RT), CNRS UMR no 3523 Chem4Life, Chemogenomic and Biological Screening platform, Université Paris Cité F-75015 Paris France
| | - Sergio Mallart
- Institut Pasteur, Department of Structural Biology and Chemistry, CNRS UMR no 3523 Chem4Life, Epigenetic Chemical Biology, Université Paris Cité F-75015 Paris France
| | - Reem K Arafa
- Drug Design and Discovery Lab, Zewail City of Science and Technology 12578 Cairo Egypt
- Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology 12578 Cairo Egypt
| | - Paola B Arimondo
- Institut Pasteur, Department of Structural Biology and Chemistry, CNRS UMR no 3523 Chem4Life, Epigenetic Chemical Biology, Université Paris Cité F-75015 Paris France
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Nas K, Güçlü E, Keskin Y, Dilek G, Kalçık Unan M, Can N, Tekeoğlu İ, Kamanlı A. Clinical course and prognostic factors of COVID-19 infection in patients with chronic inflammatory-rheumatic disease: A retrospective, case-control study. Arch Rheumatol 2023; 38:44-55. [PMID: 37235113 PMCID: PMC10208609 DOI: 10.46497/archrheumatol.2023.9289] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Accepted: 02/07/2022] [Indexed: 04/13/2024] Open
Abstract
OBJECTIVES This study aims to investigate the prognosis of novel coronavirus disease-2019 (COVID-19) infection in patients with the chronic inflammatory-rheumatic disease and evaluate the effects of immunosuppressive drugs on the prognosis, clinical characteristics, laboratory findings and hospitalization periods of the rheumatic patients with COVID-19 infection. PATIENTS AND METHODS Between April 2020 and March 2021, a total of 101 patients (30 males, 71 females; mean age: 48±14.4 years; range, 46 to 48 years) with the rheumatic diseases diagnosed with COVID-19 infection were included. A total of 102 age- and sex-matched patients (35 males, 67 females; mean age: 44±14.4 years; range, 28 to 44 years) who were diagnosed with COVID-19 infection and had no history of rheumatic disease in the same period were included as the control group. Data including demographic characteristics of the patients, presence of any symptoms of COVID-19 disease, laboratory data at the time of diagnosis, and treatments administered were collected. RESULTS The rate of hospitalization was higher in 38 (37%) patients without rheumatic diseases than in 31 (31%) patients with rheumatic diseases (p=0.324). The rate of lung infiltration on radiographic examination was higher in patients without rheumatic diseases (40% vs. 49%) (p=0.177). COVID-19 infection symptoms such as anosmia 45 (45%), ageusia 51 (50%), shortness of breath 45(45%), nausea 29 (29%), vomiting 16 (16%), diarrhea 25 (25%) and myalgia-arthralgia 81 (80%) were higher in patients with rheumatic diseases. In terms of laboratory values, lymphocyte count (p=0.031) was statistically higher in patients without rheumatic diseases. Hydroxychloroquine (35%), oseltamivir 10 (10%), antibiotics 27 (26%), acetylsalicylic acid 52 (51%), and supplementary oxygen 25 (25%) treatments which used to cure COVID 19 infection were administered more in patients without rheumatic diseases. The number of treatments administered was higher in patients without rheumatic diseases (p<0.001). CONCLUSION Patients with the chronic inflammatory-rheumatic disease have more symptoms due to COVID-19 infection, but the disease course is not poor and hospitalization rates are lower.
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Affiliation(s)
- Kemal Nas
- Department of Physical Medicine and Rehabilitation, Division of Rheumatology and Immunology, Sakarya University School of Medicine, Sakarya, Türkiye
| | - Ertuğrul Güçlü
- Department of Infectious Diseases and Clinical Microbiology, Sakarya University Faculty of Medicine, Sakarya, Türkiye
| | - Yaşar Keskin
- Department of Physical Medicine and Rehabilitation, Bezmialem Vakıf University Faculty of Medicine, Istanbul, Türkiye
| | - Gamze Dilek
- Department of Physical Medicine and Rehabilitation, Division of Rheumatology and Immunology, Sakarya University School of Medicine, Sakarya, Türkiye
| | - Mehtap Kalçık Unan
- Department of Physical Medicine and Rehabilitation, Division of Rheumatology and Immunology, Sakarya University School of Medicine, Sakarya, Türkiye
| | - Nurselin Can
- Department of Infectious Diseases and Clinical Microbiology, Sakarya University Faculty of Medicine, Sakarya, Türkiye
| | - İbrahim Tekeoğlu
- Department of Physical Medicine and Rehabilitation, Division of Rheumatology and Immunology, Sakarya University School of Medicine, Sakarya, Türkiye
| | - Ayhan Kamanlı
- Department of Physical Medicine and Rehabilitation, Division of Rheumatology and Immunology, Sakarya University School of Medicine, Sakarya, Türkiye
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21
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Panahi Y, Gorabi AM, Talaei S, Beiraghdar F, Akbarzadeh A, Tarhriz V, Mellatyar H. An overview on the treatments and prevention against COVID-19. Virol J 2023; 20:23. [PMID: 36755327 PMCID: PMC9906607 DOI: 10.1186/s12985-023-01973-9] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 01/14/2023] [Indexed: 02/10/2023] Open
Abstract
BACKGROUND The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to plague the world. While COVID-19 is asymptomatic in most individuals, it can cause symptoms like pneumonia, ARDS (acute respiratory distress syndrome), and death in others. Although humans are currently being vaccinated with several COVID-19 candidate vaccines in many countries, however, the world still is relying on hygiene measures, social distancing, and approved drugs. RESULT There are many potential therapeutic agents to pharmacologically fight COVID-19: antiviral molecules, recombinant soluble angiotensin-converting enzyme 2 (ACE2), monoclonal antibodies, vaccines, corticosteroids, interferon therapies, and herbal agents. By an understanding of the SARS-CoV-2 structure and its infection mechanisms, several vaccine candidates are under development and some are currently in various phases of clinical trials. CONCLUSION This review describes potential therapeutic agents, including antiviral agents, biologic agents, anti-inflammatory agents, and herbal agents in the treatment of COVID-19 patients. In addition to reviewing the vaccine candidates that entered phases 4, 3, and 2/3 clinical trials, this review also discusses the various platforms that are used to develop the vaccine COVID-19.
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Affiliation(s)
- Yunes Panahi
- Pharmacotherapy Department, Faculty of Pharmacy, Bagyattallah University of Medical Sciences, Tehran, Iran
| | - Armita Mahdavi Gorabi
- Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Sona Talaei
- Department of Basic Sciences, Maragheh University of Medical Sciences, Maragheh, Iran
| | - Fatemeh Beiraghdar
- Nephrology and Urology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Abolfazl Akbarzadeh
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Vahideh Tarhriz
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hassan Mellatyar
- Pharmacotherapy Department, Faculty of Pharmacy, Bagyattallah University of Medical Sciences, Tehran, Iran
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22
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Donniacuo M, De Angelis A, Rafaniello C, Cianflone E, Paolisso P, Torella D, Sibilio G, Paolisso G, Castaldo G, Urbanek K, Rossi F, Berrino L, Cappetta D. COVID-19 and atrial fibrillation: Intercepting lines. Front Cardiovasc Med 2023; 10:1093053. [PMID: 36755799 PMCID: PMC9899905 DOI: 10.3389/fcvm.2023.1093053] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 01/09/2023] [Indexed: 01/24/2023] Open
Abstract
Almost 20% of COVID-19 patients have a history of atrial fibrillation (AF), but also a new-onset AF represents a frequent complication in COVID-19. Clinical evidence demonstrates that COVID-19, by promoting the evolution of a prothrombotic state, increases the susceptibility to arrhythmic events during the infective stages and presumably during post-recovery. AF itself is the most frequent form of arrhythmia and is associated with substantial morbidity and mortality. One of the molecular factors involved in COVID-19-related AF episodes is the angiotensin-converting enzyme (ACE) 2 availability. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses ACE2 to enter and infect multiple cells. Atrial ACE2 internalization after binding to SARS-CoV-2 results in a raise of angiotensin (Ang) II, and in a suppression of cardioprotective Ang(1-7) formation, and thereby promoting cardiac hypertrophy, fibrosis and oxidative stress. Furthermore, several pharmacological agents used in COVID-19 patients may have a higher risk of inducing electrophysiological changes and cardiac dysfunction. Azithromycin, lopinavir/ritonavir, ibrutinib, and remdesivir, used in the treatment of COVID-19, may predispose to an increased risk of cardiac arrhythmia. In this review, putative mechanisms involved in COVID-19-related AF episodes and the cardiovascular safety profile of drugs used for the treatment of COVID-19 are summarized.
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Affiliation(s)
- Maria Donniacuo
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Antonella De Angelis
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Concetta Rafaniello
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Eleonora Cianflone
- Department of Medical and Surgical Sciences, Magna Græcia University, Catanzaro, Italy
| | - Pasquale Paolisso
- Cardiovascular Center Aalst, OLV Hospital, Aalst, Belgium
- Department of Advanced Biomedical Sciences, University of Naples “Federico II”, Naples, Italy
| | - Daniele Torella
- Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy
| | | | - Giuseppe Paolisso
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Giuseppe Castaldo
- Department of Molecular Medicine and Medical Biotechnology, University of Naples “Federico II”, Naples, Italy
- CEINGE Advanced Biotechnologies, Naples, Italy
| | - Konrad Urbanek
- Department of Molecular Medicine and Medical Biotechnology, University of Naples “Federico II”, Naples, Italy
- CEINGE Advanced Biotechnologies, Naples, Italy
| | - Francesco Rossi
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Liberato Berrino
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Donato Cappetta
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy
- Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, Italy
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23
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Laref S, Wang B, Gao X, Gojobori T. Computational Studies of Auto-Active van der Waals Interaction Molecules on Ultra-Thin Black-Phosphorus Film. Molecules 2023; 28:molecules28020681. [PMID: 36677738 PMCID: PMC9864666 DOI: 10.3390/molecules28020681] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 01/03/2023] [Accepted: 01/04/2023] [Indexed: 01/11/2023] Open
Abstract
Using the van der Waals density functional theory, we studied the binding peculiarities of favipiravir (FP) and ebselen (EB) molecules on a monolayer of black phosphorene (BP). We systematically examined the interaction characteristics and thermodynamic properties in a vacuum and a continuum, solvent interface for active drug therapy. These results illustrate that the hybrid molecules are enabled functionalized two-dimensional (2D) complex systems with a vigorous thermostability. We demonstrate in this study that these molecules remain flat on the monolayer BP system and phosphorus atoms are intact. It is inferred that the hybrid FP+EB molecules show larger adsorption energy due to the van der Waals forces and planar electrostatic interactions. The changes in Gibbs free energy at different surface charge fluctuations and temperatures imply that the FP and EB are allowed to adsorb from the gas phase onto the 2D film at high temperatures. Thereby, the results unveiled beneficial inhibitor molecules on two dimensional BP nanocarriers, potentially introducing a modern strategy to enhance the development of advanced materials, biotechnology, and nanomedicine.
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Affiliation(s)
- Slimane Laref
- Computational Bioscience Research Center (CBRC), King Abdullah University of Science & Technology (KAUST), Thuwal 23955-6900, Saudi Arabia
- Correspondence:
| | - Bin Wang
- School of Chemical, Biological and Materials Engineering, Center for Interfacial Reaction Engineering (CIRE), University of Oklahoma, Norman, OK 73019, USA
| | - Xin Gao
- Computational Bioscience Research Center (CBRC), King Abdullah University of Science & Technology (KAUST), Thuwal 23955-6900, Saudi Arabia
| | - Takashi Gojobori
- Computational Bioscience Research Center (CBRC), King Abdullah University of Science & Technology (KAUST), Thuwal 23955-6900, Saudi Arabia
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24
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Nivetha R, Bhuvaragavan S, Muthu Kumar T, Ramanathan K, Janarthanan S. Inhibition of multiple SARS-CoV-2 proteins by an antiviral biomolecule, seselin from Aegle marmelos deciphered using molecular docking analysis. J Biomol Struct Dyn 2022; 40:11070-11081. [PMID: 34431451 DOI: 10.1080/07391102.2021.1955009] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Our earlier experimental and computational report produced evidence on the antiviral nature of the compound seselin purified from the leaf extracts of Aegle marmelos against Bombyx mori Nuclear Polyhedrosis Virus (BmNPV). In the pandemic situation of COVID-19 caused by the SARS-COV-2 virus, an in silico effort to evaluate the potentiality of the seselin was made to test its efficacy against multiple targets of SARS-COV-2 such as spike protein S2, COVID-19 main protease and free enzyme of the SARS-CoV-2 (2019-nCoV) main protease. The ligand seselin showed the best interaction with receptors, spike protein S2, COVID-19 main protease and free enzyme of the SARS-CoV-2 (2019-nCoV) main protease with a binding energy of -6.3 kcal/mol, -6.9 kcal/mol and -6.7 kcal/mol, respectively. Docking analysis with three different receptors identified that all the computationally predicted lowest energy complexes were stabilized by intermolecular hydrogen bonds and stacking interactions. The amino acid residues involved in interactions were ASP1184, GLU1182, ARG1185 and SER943 for spike protein, SER1003, ALA958 and THR961 for COVID-19 main protease, and for SARS-CoV-2 (2019-nCoV) main protease, it was THR111, GLN110 and THR292. The MD simulation and MM/PBSA analysis showed that the compound seselin could effectively bind with the target receptors. The outcome of pharmacokinetic analysis suggested that the compound had favourable drugability properties. The results suggested that the seselin had inhibitory potential over multiple SARS-COV-2 targets and hold a high potential to work effectively as a novel drug for COVID-19 if evaluated in experimental setups in the foreseeable future. Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
| | | | - Thirunavukkarasu Muthu Kumar
- Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, India
| | - Karuppasamy Ramanathan
- Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, India
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25
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Irani AH, Steyn-Ross DA, Steyn-Ross ML, Voss L, Sleigh J. The molecular dynamics of possible inhibitors for SARS-CoV-2. J Biomol Struct Dyn 2022; 40:10023-10032. [PMID: 34229582 DOI: 10.1080/07391102.2021.1942215] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The novel coronavirus SARS-CoV-2, responsible for the present COVID-19 global pandemic, is known to bind to the angiotensin converting enzyme-2 (ACE2) receptor in human cells. A possible treatment of COVID-19 could involve blocking ACE2 and/or disabling the spike protein on the virus. Here, molecular dynamics simulations were performed to test the binding affinities of nine candidate compounds. Of these, three drugs showed significant therapeutic potential that warrant further investigation: SN35563, a ketamine ester analogue, was found to bind strongly to the ACE2 receptor but weakly within the spike receptor-binding domain (RBD); in contrast, arbidol and hydroxychloroquine bound preferentially with the spike RBD rather than ACE2. A fourth drug, remdesivir, bound approximately equally to both the ACE2 and viral spike RBD, thus potentially increasing risk of viral infection by bringing the spike protein into closer proximity to the ACE2 receptor. We suggest more experimental investigations to test that SN35563-in combination with arbidol or hydroxychloroquine-might act synergistically to block viral cell entry by providing therapeutic blockade of the host ACE2 simultaneous with reduction of viral spike receptor-binding; and that this combination therapy would allow the use of smaller doses of each drug.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Amir H Irani
- Department of Anaesthesia and Pain Medicine, Waikato District Health Board, Hamilton, New Zealand.,School of Engineering, University of Waikato, Hamilton, New Zealand
| | - D A Steyn-Ross
- School of Engineering, University of Waikato, Hamilton, New Zealand
| | | | - Logan Voss
- Department of Anaesthesiology, Waikato Clinical Campus, University of Auckland, Hamilton, New Zealand
| | - Jamie Sleigh
- Department of Anaesthesia and Pain Medicine, Waikato District Health Board, Hamilton, New Zealand
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26
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Saha L, Vij S, Rawat K. Liver injury induced by COVID 19 treatment - what do we know? World J Gastroenterol 2022; 28:6314-6327. [PMID: 36533104 PMCID: PMC9753058 DOI: 10.3748/wjg.v28.i45.6314] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 10/07/2022] [Accepted: 11/17/2022] [Indexed: 12/02/2022] Open
Abstract
The severity of coronavirus disease 2019 (COVID-19) may be correlated with the risk of liver injury development. An increasing number of studies indicate that degrees of hepatotoxicity have been associated with using some medications in the management of COVID-19 patients. However, limited studies have systematically investigated the evidence of drug-induced liver injury (DILI) in COVID-19 patients. An increasing number of studies indicate that degrees of hepatotoxicity have been associated with using some of these medications in the management of COVID-19 patients. Significantly, it was relieved after the cessation of these agents. However, to our knowledge, no studies have systematically investigated the evidence of DILI in COVID-19 patients. In this review, we discussed the association between hepatotoxicity in COVID-19 patients and the drugs used in these patients and possible mechanisms of hepatotoxicity. The currently available evidence on the association of different therapeutic agents with hepatotoxicity in COVID-19 patient was systematically reviewed.
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Affiliation(s)
- Lekha Saha
- Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Soumya Vij
- Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Kajal Rawat
- Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
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27
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Shah SMI, Yasmin F, Memon RS, Jatoi NN, Savul IS, Kazmi S, Monawwer SA, Zafar MDB, Asghar MS, Tahir MJ, Lee KY. COVID-19 and myasthenia gravis: A review of neurological implications of the SARS-COV-2. Brain Behav 2022; 12:e2789. [PMID: 36306401 PMCID: PMC9759145 DOI: 10.1002/brb3.2789] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 09/10/2022] [Accepted: 09/24/2022] [Indexed: 11/11/2022] Open
Abstract
INTRODUCTION This review highlights the potential mechanisms of neuromuscular manifestation of COVID-19, especially myasthenia gravis (MG). METHODS An extensive literature search was conducted by two independent investigators using PubMed/MEDLINE and Google Scholar from its inception to December 2020. RESULTS Exacerbations of clinical symptoms in patients of MG who were treated with some commonly used COVID-19 drugs has been reported, with updated recommendations of management of symptoms of neuromuscular disorders. Severe acute respiratory syndrome coronavirus 2 can induce the immune response to trigger autoimmune neurological disorders. CONCLUSIONS Further clinical studies are warranted to indicate and rather confirm if MG in the setting of COVID-19 can pre-existent subclinically or develop as a new-onset disease.
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Affiliation(s)
| | - Farah Yasmin
- Department of Internal Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | - Roha Saeed Memon
- Department of Internal Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | - Nadia Nazir Jatoi
- Department of Internal Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | - Ilma Saleh Savul
- Department of Internal Medicine, St. Joseph Medical Center, Houston, Texas, USA
| | - Sana Kazmi
- Department of Internal Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | | | - Muhammad Daim Bin Zafar
- Department of Internal Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | | | | | - Ka Yiu Lee
- Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, Östersund, Sweden
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28
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Abdullah Al Awadh A. Nucleotide and nucleoside-based drugs: past, present, and future. Saudi J Biol Sci 2022; 29:103481. [PMID: 36389209 PMCID: PMC9641258 DOI: 10.1016/j.sjbs.2022.103481] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 09/28/2022] [Accepted: 10/20/2022] [Indexed: 11/06/2022] Open
Abstract
Nucleotide and nucleoside-based analogue drugs are widely used for the treatment of both acute and chronic viral infections. These drugs inhibit viral replication due to one or more distinct mechanisms. It modifies the virus's genetic structure by reducing viral capacity in every replication cycle. Their clinical success has shown strong effectiveness against several viruses, including ebolavirus, hepatitis C virus, HIV, MERS, SARS-Cov, and the most recent emergent SARS-Cov2. In this review, seven different types of inhibitors have been selected that show broad-spectrum activity against RNA viruses. A detailed overview and mechanism of actionof both analogues are given, and the clinical perspectives are discussed. These inhibitors incorporated the novel SARS-CoV-2 RdRp, further terminating the polymerase activity with variable efficacy. The recent study provides a molecular basis for the inhibitory activity of virus RdRp using nucleotide and nucleoside analogues inhibitors. Furthermore, to identify those drugs that need more research and development to combat novel infections. Consequently, there is a pressing need to focus on present drugs by establishing their cell cultures. If their potencies were evidenced, then they would be explored in the future as potential therapeutics for novel outbreaks.
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29
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Roveri V, Guimarães LL, Toma W, Correia AT. Occurrence, ecological risk assessment and prioritization of pharmaceuticals and abuse drugs in estuarine waters along the São Paulo coast, Brazil. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:89712-89726. [PMID: 35857165 PMCID: PMC9297060 DOI: 10.1007/s11356-022-21945-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 07/06/2022] [Indexed: 06/15/2023]
Abstract
The pollution of the surface waters by pharmaceuticals and personal care products (PPCPs) has attracted worldwide attention, but data regarding their occurrence and potential risks for the aquatic biota on tropical coastal rivers of South America are still scarce. In this context, the occurrence and the preliminary ecological risk assessment of eleven pharmaceuticals of various therapeutic classes (including cocaine and its primary metabolite, benzoylecgonine) were investigated, for the first time, in five rivers of São Paulo, southeast Brazil, covering a coastline of about 140 km, namely Perequê River, Itinga River, Mongaguá River, Itanhaém River and Guaraú River. Although these five rivers are born in well-preserved areas of the Atlantic rainforest biome, on its way to sea and when they cross the urban perimeter, they receive untreated sewage discharges containing a complex mixture of contaminants. In addition, a "persistence, bioaccumulation and toxicity" (PBT) approach allowed to pre-select the priority PPCPs to be monitored in this coastline. Identification of several PPCPs in the samples was done using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Ten PPCPs were successfully quantified in all five rivers, namely caffeine (9.00-560.00 ng/L), acetaminophen (
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Affiliation(s)
- Vinicius Roveri
- Universidade Metropolitana de Santos (UNIMES), Avenida Conselheiro Nébias, 536 - Encruzilhada, 11045-002, Santos, São Paulo, Brazil
- Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Avenida General Norton de Matos S/N, 4450-208, Matosinhos, Portugal
| | - Luciana Lopes Guimarães
- Laboratório de Pesquisa em Produtos Naturais, Universidade Santa Cecília, Rua Cesário Mota 8, F83A, 11045-040 Santos, São Paulo, Brazil
| | - Walber Toma
- Laboratório de Pesquisa em Produtos Naturais, Universidade Santa Cecília, Rua Cesário Mota 8, F83A, 11045-040 Santos, São Paulo, Brazil
| | - Alberto Teodorico Correia
- Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Avenida General Norton de Matos S/N, 4450-208, Matosinhos, Portugal.
- Faculdade de Ciências da Saúde da Universidade Fernando Pessoa (FCS-UFP), Rua Carlos da Maia 296, 4200-150, Porto, Portugal.
- Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira 228, 4050-313, Porto, Portugal.
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30
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The Safety Profile of COVID-19 Vaccines in Patients Diagnosed with Multiple Sclerosis: A Retrospective Observational Study. J Clin Med 2022; 11:jcm11226855. [PMID: 36431332 PMCID: PMC9692274 DOI: 10.3390/jcm11226855] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 11/14/2022] [Accepted: 11/17/2022] [Indexed: 11/22/2022] Open
Abstract
In the current COVID-19 pandemic, patients diagnosed with multiple sclerosis (MS) are considered to be one of the highest priority categories, being recognized as extremely vulnerable people. For this reason, mRNA-based COVID-19 vaccines are strongly recommended for these patients. Despite encouraging results on the efficacy and safety profile of mRNA-based COVID-19 vaccines, to date, in frail populations, including patients diagnosed with MS, this information is rather limited. We carried out a retrospective observational study with the aim to evaluate the safety profile of mRNA-based COVID-19 vaccines by retrieving real-life data of MS patients who were treated and vaccinated at the Multiple Sclerosis Center of the Hospital A.O.R.N. A. Cardarelli. Three-hundred and ten medical records of MS patients who received the first dose of the mRNA-based COVID-19 vaccine were retrieved (63% female; mean age: 45.9 years). Of these patients, 288 also received the second dose. All patients received the Pfizer-BioNTech vaccine. Relapsing-Remitting Multiple Sclerosis (RRSM) was the most common form of MS. The Expanded Disability Status Scale (EDSS) values were <3.0 in 70% of patients. The majority of patients received a Disease Modifying Therapy (DMT) during the study period, mainly interferon beta 1-a, dimethyl fumarate, and natalizumab and fingolimod. Overall, 913 AEFIs were identified, of which 539 were after the first dose of the vaccine and 374 after the second dose. The majority of these AEFIs were classified as short-term since they occurred within the first 72 h. The most common identified adverse events were pain at injection site, flu-like symptoms, and headache. Fever was reported more frequently after the second dose than after the first dose. SARS-CoV-2 infection occurred in 3 patients after the first dose. Using historical data of previous years (2017−2020), the relapses’ rate during 2021 was found to be lower. Lastly, the results of the multivariable analysis that assessed factors associated with the occurrence of AEFIs revealed a statistical significance for age, sex, and therapy with ocrelizumab (p < 0.05). In conclusion, our results indicated that Pfizer-BioNTech vaccine was safe for MS patients, being associated with AEFIs already detected in the general population. Larger observational studies with longer follow-up and epidemiological studies are strongly needed.
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Tarek Mahmoud S, Moffid MA, Sayed RM, Mostafa EA. Core shell stationary phase for a novel separation of some COVID-19 used drugs by UPLC-MS/MS Method: Study of grapefruit consumption impact on their pharmacokinetics in rats. Microchem J 2022; 181:107769. [PMID: 35855210 PMCID: PMC9284531 DOI: 10.1016/j.microc.2022.107769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 06/11/2022] [Accepted: 07/06/2022] [Indexed: 12/15/2022]
Abstract
A sensitive and selective UPLC-MS/MS method was developed for the synchronized determination of four drugs used in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), namely, azithromycin, apixaban, dexamethasone, and favipiravir in rat plasma. using a Poroshell 120 EC-C18 column (50 mm × 4.6 mm, 2.7 m) with a high-resolution ESI tandem mass spectrometer detection with multiple reaction monitoring. We used an Agilent Poroshell column, which is characterized by a stationary phase based on non-porous core particles. With a remarkable improvement in the number of theoretical plates and low column backpressure. In addition, the developed method was employed in studying the potential food-drug interaction of grapefruit juice (GFJ) with the selected drugs which affects their pharmacokinetics in rats. The LC-MS/MS operated in positive and negative ionization mode using two internal standards: moxifloxacin and chlorthalidone, respectively. Liquid- liquid extraction of the cited drugs from rat plasma was accomplished using diethyl ether: dichloromethane (70:30, v/v). The analytes were separated using methanol: 0.1 % formic acid in water (95: 5, v/v) as a mobile phase in isocratic mode of elution pumped at a flow rate of 0.3 mL/min. A detailed validation of the bio-analytical method was performed in accordance with US-FDA and EMA guidelines. Concerning the in vivo pharmacokinetic study, the statistical significance between the results of the test groups receiving GFJ along with the cited drugs and the control group was assessed demonstrating that GFJ increased the plasma concentration of azithromycin, apixaban, and dexamethasone. Accordingly, this food-drug interaction requires cautious ingestion of GFJ in patients using (SARS-CoV-2) medications as it can produce negative effects in the safety of the drug therapy. A potential drug-drug interaction is also suggested between those medications requiring a suitable dose adjustment.
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Affiliation(s)
- Sally Tarek Mahmoud
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo 11562, Egypt
| | - Marwa A Moffid
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo 11562, Egypt
| | - Rawda M Sayed
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo 11562, Egypt
| | - Eman A Mostafa
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo 11562, Egypt
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Martínez Rolando L, Villafañe JH, Cercadillo García S, Sanz Argüello A, Villanueva Rosa M, Sánchez Romero EA. Multicomponent Exercise Program to Improve the Immediate Sequelae of COVID-19: A Prospective Study with a Brief Report of 2-Year Follow-Up. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:12396. [PMID: 36231696 PMCID: PMC9566039 DOI: 10.3390/ijerph191912396] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 09/18/2022] [Accepted: 09/26/2022] [Indexed: 05/10/2023]
Abstract
COVID-19 placed teams of professionals in a hostile and unfamiliar environment where the lack of knowledge of its pathology led to the adaptation of programs used so far for other conditions to try to address the immediate sequelae of COVID-19 infection. That is why the aim of this study was to assess the effects of a multicomponent exercise program (MEP) in improving cardio-respiratory performance, health status, disability due to dyspnea, aerobic capacity and endurance, and the immediate sequelae of COVID-19. Thirty-nine patients referred from different hospital services were included in this study. An intervention of seven weeks with sessions twice a week was carried out, where patients underwent intervallic training sessions followed by strengthening exercises and individualized respiratory physiotherapy exercises. The results of this study show a significant improvement in cardio-respiratory performance, health status, disability due to dyspnea, and aerobic capacity and endurance after intervention; and an increase in health status and reduction in disability due to dyspnea at the 2-year follow-up. In addition, none of the patients had any adverse effects either pre-post treatment or at the 2-year follow-up. Individualized and monitored MEP in survivors of COVID-19 showed positive effects in a pre-post evaluation and the 2-year follow up, improving the immediate sequelae of post-COVID-19 patients. This highlights the importance of the professional background of the rehabilitation teams in adapting to an unknown clinical environment.
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Affiliation(s)
- Lidia Martínez Rolando
- Department of Physiotherapy, Faculty of Sport Sciences, Universidad Europea de Madrid, 28670 Villaviciosa de Odón, Spain
- Musculoskeletal Pain and Motor Control Research Group, Faculty of Sport Sciences, Universidad Europea de Madrid, 28670 Villaviciosa de Odón, Spain
- Department of Physiotherapy, Faculty of Health Sciences, Universidad Europea de Canarias, 38300 Santa Cruz de Tenerife, Spain
- Musculoskeletal Pain and Motor Control Research Group, Faculty of Health Sciences, Universidad Europea de Canarias, 38300 Santa Cruz de Tenerife, Spain
- Rey Juan Carlos University Hospital of Móstoles, 28933 Madrid, Spain
| | | | - Soledad Cercadillo García
- Musculoskeletal Pain and Motor Control Research Group, Faculty of Sport Sciences, Universidad Europea de Madrid, 28670 Villaviciosa de Odón, Spain
- Musculoskeletal Pain and Motor Control Research Group, Faculty of Health Sciences, Universidad Europea de Canarias, 38300 Santa Cruz de Tenerife, Spain
- Rey Juan Carlos University Hospital of Móstoles, 28933 Madrid, Spain
| | - Ana Sanz Argüello
- Musculoskeletal Pain and Motor Control Research Group, Faculty of Sport Sciences, Universidad Europea de Madrid, 28670 Villaviciosa de Odón, Spain
- Musculoskeletal Pain and Motor Control Research Group, Faculty of Health Sciences, Universidad Europea de Canarias, 38300 Santa Cruz de Tenerife, Spain
- Rey Juan Carlos University Hospital of Móstoles, 28933 Madrid, Spain
| | - Marta Villanueva Rosa
- Musculoskeletal Pain and Motor Control Research Group, Faculty of Sport Sciences, Universidad Europea de Madrid, 28670 Villaviciosa de Odón, Spain
- Musculoskeletal Pain and Motor Control Research Group, Faculty of Health Sciences, Universidad Europea de Canarias, 38300 Santa Cruz de Tenerife, Spain
- Rey Juan Carlos University Hospital of Móstoles, 28933 Madrid, Spain
| | - Eleuterio A. Sánchez Romero
- Department of Physiotherapy, Faculty of Sport Sciences, Universidad Europea de Madrid, 28670 Villaviciosa de Odón, Spain
- Musculoskeletal Pain and Motor Control Research Group, Faculty of Sport Sciences, Universidad Europea de Madrid, 28670 Villaviciosa de Odón, Spain
- Department of Physiotherapy, Faculty of Health Sciences, Universidad Europea de Canarias, 38300 Santa Cruz de Tenerife, Spain
- Musculoskeletal Pain and Motor Control Research Group, Faculty of Health Sciences, Universidad Europea de Canarias, 38300 Santa Cruz de Tenerife, Spain
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Ruggiero R, Balzano N, Di Napoli R, Mascolo A, Berrino PM, Rafaniello C, Sportiello L, Rossi F, Capuano A. Capillary leak syndrome following COVID-19 vaccination: Data from the European pharmacovigilance database Eudravigilance. Front Immunol 2022; 13:956825. [PMID: 36177033 PMCID: PMC9513245 DOI: 10.3389/fimmu.2022.956825] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 08/23/2022] [Indexed: 11/13/2022] Open
Abstract
Capillary leak syndrome (CLS) emerged as new adverse event after immunization (AEFI) associated to COVID-19 vaccination. CLS is a rare condition characterized by increased capillary permeability, resulting in hypoalbuminemia, hypotension, and edema mainly in the upper and lower limbs. Our pharmacovigilance study aims to evaluate the CLS onset following receipt of COVID-19 mRNA vaccines (mRNA-1273 and BNT162b2) compared to viral vector vaccines (Ad26.COV2-S and ChAdOx1-SARS-COV-2). We carried a cross-sectional study using all Individual Case Safety Reports (ICSRs) reporting a COVID-19 vaccine as suspected drug and CLS as AEFI, which were collected in the pharmacovigilance database EudraVigilance from January 1st, 2021, to January 14th, 2022. We applied the Reporting Odds Ratio (ROR) 95% CI for the disproportionality analysis. During our study period, CLS was described as AEFI in 84 out of 1,357,962 ICRs reporting a vaccine COVID-19 as suspected drug and collected in the EV database. Overall, the ICSR reported by CLS were mainly related to the viral vector COVID-19(ChAdOx1-SARS-COV-2 = 36; Ad26.COV2-S = 9). The mRNA COVID-19 vaccines were reported in 39 ICSRs (BNT162b2 =33; mRNA-1273 =6). Majority of ICSRs were reported by healthcare professionals (71.4%). Majority of the patients were adult (58.3%) and the female gender accounted in more than 65% of ICSRs referred both to classes vaccines. In particular, women were more represented in ICSRs referred to mRNA-1273 (83.3%) and to ChAdOx1-SARS-COV-2 (72.2%). The CLS outcome was more frequently favorable in mRNA ICSRs (33,3%) than the viral vector ones (13.3%). Among the ICSRs reporting CLS with unfavorable outcome, we found also 9 fatal cases (BNT162b2 = 1; ChAdOx1-SARS-COV-2 = 4; Ad26.COV2-S = 4). From disproportionality analysis emerged a lower CLS reporting probability after vaccination with mRNA vaccines compared to viral vector-based ones (ROR 0.5, 95% CI 0.3-0.7; p <0.001).Our findings, even if subject to the limitations of spontaneous reporting systems, suggest a small but statistically significant safety concern for CLS following receipt of COVID-19 viral vector vaccines, in particular with Ad26.COV2-S. Cytokine-release following T-cell activation could be involved in CLS occurrence, but a precise mechanism has been not yet identified. COVID-19 vaccines remain attentive as possible triggers of CLS.
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Affiliation(s)
- Rosanna Ruggiero
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, University of Campania “L. Vanvitelli”, Naples, Italy
- Department of Experimental Medicine – Section of Pharmacology “L. Donatelli”, University of Campania “L. Vanvitelli”, Naples, Italy
| | - Nunzia Balzano
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, University of Campania “L. Vanvitelli”, Naples, Italy
- Department of Experimental Medicine – Section of Pharmacology “L. Donatelli”, University of Campania “L. Vanvitelli”, Naples, Italy
| | - Raffaella Di Napoli
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, University of Campania “L. Vanvitelli”, Naples, Italy
- Department of Experimental Medicine – Section of Pharmacology “L. Donatelli”, University of Campania “L. Vanvitelli”, Naples, Italy
| | - Annamaria Mascolo
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, University of Campania “L. Vanvitelli”, Naples, Italy
- Department of Experimental Medicine – Section of Pharmacology “L. Donatelli”, University of Campania “L. Vanvitelli”, Naples, Italy
| | - Pasquale Maria Berrino
- Department of Specialized Medicine, Diagnostic and Experimental, University of Bologna “Alma Mater Studiorum”, Bologna, Italy
| | - Concetta Rafaniello
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, University of Campania “L. Vanvitelli”, Naples, Italy
- Department of Experimental Medicine – Section of Pharmacology “L. Donatelli”, University of Campania “L. Vanvitelli”, Naples, Italy
| | - Liberata Sportiello
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, University of Campania “L. Vanvitelli”, Naples, Italy
- Department of Experimental Medicine – Section of Pharmacology “L. Donatelli”, University of Campania “L. Vanvitelli”, Naples, Italy
| | - Francesco Rossi
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, University of Campania “L. Vanvitelli”, Naples, Italy
- Department of Experimental Medicine – Section of Pharmacology “L. Donatelli”, University of Campania “L. Vanvitelli”, Naples, Italy
| | - Annalisa Capuano
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, University of Campania “L. Vanvitelli”, Naples, Italy
- Department of Experimental Medicine – Section of Pharmacology “L. Donatelli”, University of Campania “L. Vanvitelli”, Naples, Italy
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Kaur I, Behl T, Sehgal A, Singh S, Sharma N, Subramanian V, Fuloria S, Fuloria NK, Sekar M, Dailah HG, Alsubayiel AM, Bhatia S, Al-Harrasi A, Aleya L, Bungau S. A motley of possible therapies of the COVID-19: reminiscing the origin of the pandemic. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:67685-67703. [PMID: 35933528 PMCID: PMC9362373 DOI: 10.1007/s11356-022-22345-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Accepted: 07/28/2022] [Indexed: 05/20/2023]
Abstract
The 2019 outbreak of corona virus disease began from Wuhan (China), transforming into a leading pandemic, posing an immense threat to the global population. The WHO coined the term nCOVID-19 for the disease on 11th February, 2020 and the International Committee of Taxonomy of Viruses named it SARS-CoV-2, on account of its similarity with SARS-CoV-1 of 2003. The infection is associated with fever, cough, pneumonia, lung damage, and ARDS along with clinical implications of lung opacities. Brief understanding of the entry target of virus, i.e., ACE2 receptors has enabled numerous treatment options as discussed in this review. The manuscript provides a holistic picture of treatment options in COVID-19, such as non-specific anti-viral drugs, immunosuppressive agents, anti-inflammatory candidates, anti-HCV, nucleotide inhibitors, antibodies and anti-parasitic, RNA-dependent RNA polymerase inhibitors, anti-retroviral, vitamins and hormones, JAK inhibitors, and blood plasma therapy. The text targets to enlist the investigations conducted on all the above categories of drugs, with respect to the COVID-19 pandemic, to accelerate their significance in hindering the disease progression. The data collected primarily targets recently published articles and most recent records of clinical trials, focusing on the last 10-year database. The current review provides a comprehensive view on the critical need of finding a suitable treatment for the currently prevalent COVID-19 disease, and an opportunity for the researchers to investigate the varying possibilities to find and optimized treatment approach to mitigate and ameliorate the chaos created by the pandemic worldwide.
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Affiliation(s)
- Ishnoor Kaur
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Tapan Behl
- Chitkara College of Pharmacy, Chitkara University, Punjab, India.
| | - Aayush Sehgal
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Sukhbir Singh
- MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala, Haryana, 133207, India
| | - Neelam Sharma
- MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala, Haryana, 133207, India
| | | | - Shivkanya Fuloria
- Faculty of Pharmacy & Center of Excellence for Biomaterials Engineering, AIMST University, Bedong, Kedah, Malaysia
| | - Neeraj Kumar Fuloria
- Faculty of Pharmacy & Center of Excellence for Biomaterials Engineering, AIMST University, Bedong, Kedah, Malaysia
| | - Mahendran Sekar
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur, Royal College of Medicine, Perak, Ipoh, Malaysia
| | - Hamed Ghaleb Dailah
- Research and Scientific Studies Unit, College of Nursing, Jazan University, Jazan, Saudi Arabia
| | - Amal M Alsubayiel
- Department of Pharmaceutics, College of Pharmacy, Qassim University, Buraydah, Kingdom of Saudi Arabia
| | - Saurabh Bhatia
- Natural & Medical Sciences Research Center, University of Nizwa, Nizwa, Oman
- School of Health Science, University of Petroleum and Energy Studies, Dehradun, Uttarakhand, India
| | - Ahmed Al-Harrasi
- Natural & Medical Sciences Research Center, University of Nizwa, Nizwa, Oman
| | - Lotfi Aleya
- Chrono-Environment Laboratory, UMR CNRS 6249, Bourgogne Franche-Comté University, Besançon, France
| | - Simona Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania
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Asmarian N, Zand F, Delavari P, Khaloo V, Esmaeilinezhad Z, Sabetian G, Moeini Y, Savaie M, Javaherforooshzadeh F, Soltani F, Yousefi F, Heidari Sardabi E, Haddadzadeh Shoushtari M, Dehnadi Moghadam A, Dehnadi Moghadam F, Gholami S. Predictors of Intensive Care Unit Admission in Patients with Confirmed Coronavirus Disease 2019: A Cross-Sectional Study. IRANIAN JOURNAL OF MEDICAL SCIENCES 2022; 47:450-460. [PMID: 36117577 PMCID: PMC9445874 DOI: 10.30476/ijms.2021.89916.2068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 05/10/2021] [Accepted: 08/13/2021] [Indexed: 01/08/2023]
Abstract
Background The coronavirus disease 2019 (COVID-19) has become the leading source of pneumonia outbreaks in the world. The present study aimed to compare the condition of intensive care unit (ICU) and non-ICU COVID-19 patients in terms of epidemiological and clinical features, laboratory findings, and outcomes in three cities across Iran. Methods In a cross-sectional study, 195 COVID-19 patients admitted to five hospitals across Iran during March-April 2020 were recruited. Collected information included demographic data, laboratory findings, symptoms, medical history, and outcomes. Data were analyzed using SPSS software with t test or Mann-Whitney U test (continuous data) and Chi square test or Fisher's exact test (categorical variables). P<0.05 was considered statistically significant. Results Of the 195 patients, 57.4% were men, and 67.7% had at least one comorbidity. The prevalence of stroke, chronic obstructive pulmonary disease, and autoimmune diseases was higher in ICU than in non-ICU patients (P=0.042, P=0.020, and P=0.002, respectively). Compared with non-ICU, ICU patients had significantly higher white blood cell (WBC) count (P=0.008), cardiac troponin concentrations (P=0.040), lactate dehydrogenase levels (P=0.027), erythrocyte sedimentation rates (P=0.008), and blood urea nitrogen (BUN) (P=0.029), but lower hematocrit levels (P=0.001). The mortality rate in ICU and non-ICU patients was 48.1% and 6.1%, respectively. The risk factors for mortality included age>40 years, body mass index<18 Kg/m2, hypertension, coronary artery disease, fever, cough, dyspnea, ST-segment changes, pericardial effusion, and a surge in WBC and C-reactive protein, aspartate aminotransferase, and BUN. Conclusion A high index of suspicion for ICU admission should be maintained in patients with positive clinical and laboratory predictive factors.
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Affiliation(s)
- Naeimehossadat Asmarian
- Anesthesiology and Critical Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Farid Zand
- Anesthesiology and Critical Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Parvin Delavari
- Nursing Care Research Center, School of Nursing and Midwifery, Semnan University of Medical Sciences, Semnan, Iran
| | - Vahid Khaloo
- Hazrate Ali-Asghar Teaching Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zahra Esmaeilinezhad
- Anesthesiology and Critical Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Golnar Sabetian
- Trauma Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Yaldasadat Moeini
- Anesthesiology and Critical Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohsen Savaie
- Pain Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | | | - Farhad Soltani
- Pain Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Farid Yousefi
- Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ebrahim Heidari Sardabi
- Atherosclerosis Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Maryam Haddadzadeh Shoushtari
- Air Pollution and Respiratory Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | | | | | - Somayeh Gholami
- Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran
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Chavda VP, Chen Y, Dave J, Chen ZS, Chauhan SC, Yallapu MM, Uversky VN, Bezbaruah R, Patel S, Apostolopoulos V. COVID-19 and vaccination: myths vs science. Expert Rev Vaccines 2022; 21:1603-1620. [PMID: 35980281 DOI: 10.1080/14760584.2022.2114900] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Several vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed since the inception of the coronavirus disease 2019 (COVID-19) in December 2019, at unprecedented speed. However, these rapidly developed vaccines raised many questions related to the efficacy and safety of vaccines in different communities across the globe. Various hypotheses regarding COVID-19 and its vaccines were generated, and many of them have also been answered with scientific evidence. Still, there are many myths/misinformation related to COVID-19 and its vaccines, which create hesitancy for COVID-19 vaccination, and must be addressed critically to achieve success in the battle against the pandemic. AREA COVERED The development of anti-SARS-CoV-2 vaccines against COVID-19, their safety and efficacy, and myths/misinformation relating to COVID-19 and vaccines are presented. EXPERT OPINION In this pandemic we have seen a global collaborative effort of researchers, governments, and industry, supported by billions of dollars in funding, have allowed the development of vaccines far more quickly than in the past. Vaccines go through rigorous testing, analysis, and evaluations in clinical settings prior to their approval, even if they are approved for emergency use. Despite the myths, vaccination represents an important strategy to get back to normality.
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Affiliation(s)
- Vivek P Chavda
- Department of Pharmaceutics and Pharmaceutical Technology, L.M. College of Pharmacy, Ahmedabad
| | - Yangmin Chen
- Peter J. Tobin College of Business, St. John's University, Queens, NY 11439, USA
| | - Jayant Dave
- Department of Pharmaceutical Quality Assurance, L.M. College of Pharmacy, Ahmedabad
| | - Zhe-Sheng Chen
- College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA
| | - Subhash C Chauhan
- Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX, USA.,South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX, USA
| | - Murali M Yallapu
- Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX, USA.,South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX, USA
| | - Vladimir N Uversky
- Department of Molecular Medicine and Byrd Alzheimer's Research Institure, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
| | - Rajashri Bezbaruah
- Department of Pharmaceutical Sciences, Faculty of Science and Engineering, Dibrugarh University, Dibrugarh -786004, Assam, India
| | - Sandip Patel
- Department of Pharmacology, L.M. College of Pharmacy, Ahmedabad
| | - Vasso Apostolopoulos
- Institute for Health and Sport, Immunology and Translational Research Group, Victoria University, Melbourne, VIC, 3030, Australia.,Immunology Program, Australian Institute for Musculoskeletal Science (AIMSS), Melbourne, VIC, 3021, Australia
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Vai B, Mazza MG, Marisa CD, Beezhold J, Kärkkäinen H, Saunders J, Samochowiec J, Benedetti F, Leboyer M, Fusar-Poli P, De Picker L. Joint European policy on the COVID-19 risks for people with mental disorders: An umbrella review and evidence- and consensus-based recommendations for mental and public health. Eur Psychiatry 2022; 65:e47. [PMID: 35971656 PMCID: PMC9486830 DOI: 10.1192/j.eurpsy.2022.2307] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 07/18/2022] [Accepted: 07/23/2022] [Indexed: 11/23/2022] Open
Abstract
As COVID-19 becomes endemic, identifying vulnerable population groups for severe infection outcomes and defining rapid and effective preventive and therapeutic strategies remains a public health priority. We performed an umbrella review, including comprehensive studies (meta-analyses and systematic reviews) investigating COVID-19 risk for infection, hospitalization, intensive care unit (ICU) admission, and mortality in people with psychiatric disorders, and outlined evidence- and consensus-based recommendations for overcoming potential barriers that psychiatric patients may experience in preventing and managing COVID-19, and defining optimal therapeutic options and current research priorities in psychiatry. We searched Web of Science, PubMed, and Ovid/PsycINFO databases up to 17 January 2022 for the umbrella review. We synthesized evidence, extracting when available pooled odd ratio estimates for the categories "any mental disorder" and "severe mental disorders." The quality of each study was assessed using the AMSTAR-2 approach and ranking evidence quality. We identified four systematic review/meta-analysis combinations, one meta-analysis, and three systematic reviews, each including up to 28 original studies. Although we rated the quality of studies from moderate to low and the evidence ranged from highly suggestive to non-significant, we found consistent evidence that people with mental illness are at increased risk of COVID-19 infection, hospitalization, and most importantly mortality, but not of ICU admission. The risk and the burden of COVID-19 in people with mental disorders, in particular those with severe mental illness, can no longer be ignored but demands urgent targeted and persistent action. Twenty-two recommendations are proposed to facilitate this process.
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Affiliation(s)
- Benedetta Vai
- Psychiatry & Clinical Psychology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
- University Vita-Salute San Raffaele, Milan, Italy
| | - Mario Gennaro Mazza
- Psychiatry & Clinical Psychology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
- University Vita-Salute San Raffaele, Milan, Italy
| | - Casanova Dias Marisa
- Section of Women’s Mental Health, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
- Department of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK
| | - Julian Beezhold
- Norwich Medical School, University of East Anglia, Norwich, United Kingdom
- Hellesdon Hospital, Norfolk and Suffolk NHS Foundation Trust, Norwich, United Kingdom
| | | | | | - Jerzy Samochowiec
- Department of Psychiatry, Pomeranian Medical University, Szczecin, Poland
| | - Francesco Benedetti
- Psychiatry & Clinical Psychology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
- University Vita-Salute San Raffaele, Milan, Italy
| | - Marion Leboyer
- Université Paris Est Créteil, INSERM U955, Laboratoire Neuro-Psychiatrie Translationnelle, Fondation FondaMental, Creteil, France
- AP-HP, Hôpital Henri Mondor, Departement Medico-Universitaire de Psychiatrie et d’Addictologie (DMU IMPACT), Federation Hospitalo-Universitaire de Médecine de Precision (FHU ADAPT), Paris, France
| | - Paolo Fusar-Poli
- Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, United Kingdom
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
| | - Livia De Picker
- University Psychiatric Hospital Campus Duffel, Duffel, Belgium
- Collaborative Antwerp Psychiatric Research Institute, University of Antwerp, Antwerp, Belgium
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Roveri V, Guimarães LL, Toma W, Correia AT. Occurrence of pharmaceuticals and cocaine in the urban drainage channels located on the outskirts of the São Vicente Island (São Paulo, Brazil) and related ecological risk assessment. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:57931-57945. [PMID: 35359205 PMCID: PMC8970415 DOI: 10.1007/s11356-022-19736-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 03/11/2022] [Indexed: 05/03/2023]
Abstract
"Wealth by the sea and poverty away from the sea breeze" is a metaphor that mirrors what happens along the Brazilian coastal zone, namely in São Vicente Island, São Paulo, Brazil. Due to the high cost of the properties on this shore, the impoverished population started to migrate to the northern outskirts of the island (away from the tourist beaches), potentiating the emergence of poor housing conditions, namely stilt-house slums. Consequently, the urban drainage channels across these outskirts neighbourhoods are potentially contaminated by human wastes. In this context, the occurrence and preliminary ecological risk assessment of eleven pharmaceuticals of various therapeutic classes (including cocaine and its primary metabolite, benzoylecgonine) were investigated, for the first time, in five urban drainage channels whose diffuse loads flow continuously to the estuarine waters of São Vicente Island. The results showed the widespread presence of these environmental stressors in all urban channels analysed, namely losartan (7.3-2680.0 ng/L), caffeine (314.0-726.0 ng/L), acetaminophen (7.0-78.2 ng/L), atenolol (6.2-23.6 ng/L), benzoylecgonine (10.2-17.2 ng/L), furosemide (1.0-7.2 ng/L), cocaine (2.3-6.7 ng/L), carbamazepine (0.2-2.6 ng/L), diclofenac (1.1-2.5 ng/L), orphenadrine (0.2-1.1 ng/L) and chlortalidone (0.5-1.0 ng/L). The overall total estimated load of pharmaceuticals and personal care products flowing to the estuarine waters of São Vicente Island is on the order of 41.1 g/day. The ecological risk assessment revealed a great environmental concern for São Vicente Island, ranging between low (e.g. carbamazepine and cocaine) and moderate to high (e.g. caffeine, acetaminophen and losartan) threats for the aquatic biota. Therefore, initiatives promoting basic sanitation, land-use regularisation and population awareness are highly recommended.
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Affiliation(s)
- Vinicius Roveri
- Universidade Metropolitana de Santos (UNIMES), Avenida Conselheiro Nébias, 536 - Encruzilhada, Santos, São Paulo, 11045-002, Brazil
- Centro Interdisciplinar de Investigação Marinha E Ambiental (CIIMAR/CIMAR), Avenida General Norton de Matos S/N, 4450-208, Matosinhos, Portugal
| | - Luciana Lopes Guimarães
- Laboratório de Pesquisa Em Produtos Naturais, Universidade Santa Cecília (UNISANTA), Rua Cesário Mota 8, Santos, São Paulo, F83A, 11045-040, Brazil
| | - Walber Toma
- Laboratório de Pesquisa Em Produtos Naturais, Universidade Santa Cecília (UNISANTA), Rua Cesário Mota 8, Santos, São Paulo, F83A, 11045-040, Brazil
| | - Alberto Teodorico Correia
- Centro Interdisciplinar de Investigação Marinha E Ambiental (CIIMAR/CIMAR), Avenida General Norton de Matos S/N, 4450-208, Matosinhos, Portugal.
- Faculdade de Ciências da Saúde da, Universidade Fernando Pessoa (FCS-UFP), Rua Carlos da Maia 296, 4200-150, Porto, Portugal.
- Instituto de Ciências Biomédicas Abel Salazar da Universidade Do Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira 228, 4050-313, Porto, Portugal.
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Ruiz-Fresneda MA, Ruiz-Pérez R, Ruiz-Fresneda C, Jiménez-Contreras E. Differences in Global Scientific Production Between New mRNA and Conventional Vaccines Against COVID-19. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:57054-57066. [PMID: 35731431 PMCID: PMC9213638 DOI: 10.1007/s11356-022-21553-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Accepted: 06/14/2022] [Indexed: 06/15/2023]
Abstract
The search for effective vaccines to stop the COVID-19 pandemic has led to an unprecedented amount of global scientific production and activity. This study aimed to analyze global scientific production on the different vaccine types (mRNA and conventional) that were validated for COVID-19 during the years 2020-2021. The scientific production generated on COVID-19 vaccines during the period 2020-2021 totaled the enormous amount of 20,459 studies published. New mRNA vaccines clearly showed higher production levels than conventional vaccines (viral and inactivated vectors), with 786 and 350 studies, respectively. The USA is the undisputed leader in the global production on COVID-19 vaccines, with Israel and Italy also playing an important role. Among the journals publishing works in this field, the New England Journal of Medicine, the British Medical Journal, and Vaccines stand out from the rest as the most important. The keyword 'immunogenicity' and its derivatives have been more researched for the new mRNA vaccines, while thrombosis has been more studied for conventional vaccines. The massive scientific production generated on COVID-19 vaccines in only two years has shown the enormous gravity of the pandemic and the extreme urgency to find a solution. This high scientific production and the main keywords found for the mRNA vaccines indicate the great potential that these vaccines have against COVID-19 and future infectious diseases. Moreover, this study provides valuable information for guiding future research lines and promoting international collaboration for an effective solution.
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Affiliation(s)
| | - Rafael Ruiz-Pérez
- Department of Information and Communication Sciences, University of Granada, 18071, Granada, Spain
| | - Carlos Ruiz-Fresneda
- Department of Information and Communication Sciences, University of Granada, 18071, Granada, Spain
- EC3metrics Spin-Off, University of Granada, 18071, Granada, Spain
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COVID-19 Update: The Golden Time Window for Pharmacological Treatments and Low Dose Radiation Therapy. RADIATION 2022. [DOI: 10.3390/radiation2030020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
At the beginning of the COVID-19 emergence, many scientists believed that, thanks to the proofreading enzyme of SARS-CoV-2, the virus would not have many mutations. Our team introduced the concept of radiation at extremely low doses in an attempt to establish selected pressure-free treatment approaches for COVID-19. The capacity of low-dose radiation to modulate excessive inflammatory responses, optimize the immune system, prevent the occurrence of dangerous cytokine storm, regulate lymphocyte counts, and control bacterial co-infections as well as different modalities were proposed as a treatment program for patients with severe COVID-19-associated pneumonia. There is now substantial evidence which indicates that it would be unwise not to further investigate low-dose radiation therapy (LDRT) as an effective remedy against COVID-19-associated pneumonia.
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Mota CM, Madden CJ. Neural circuits mediating circulating interleukin-1β-evoked fever in the absence of prostaglandin E2 production. Brain Behav Immun 2022; 103:109-121. [PMID: 35429606 PMCID: PMC9524517 DOI: 10.1016/j.bbi.2022.04.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 03/31/2022] [Accepted: 04/10/2022] [Indexed: 10/18/2022] Open
Abstract
Infectious diseases and inflammatory conditions recruit the immune system to mount an appropriate acute response that includes the production of cytokines. Cytokines evoke neurally-mediated responses to fight pathogens, such as the recruitment of thermoeffectors, thereby increasing body temperature and leading to fever. Studies suggest that the cytokine interleukin-1β (IL-1β) depends upon cyclooxygenase (COX)-mediated prostaglandin E2 production for the induction of neural mechanisms to elicit fever. However, COX inhibitors do not eliminate IL-1β-induced fever, thus suggesting that COX-dependent and COX-independent mechanisms are recruited for increasing body temperature after peripheral administration of IL-1β. In the present study, we aimed to build a foundation for the neural circuit(s) controlling COX-independent, inflammatory fever by determining the involvement of brain areas that are critical for controlling the sympathetic outflow to brown adipose tissue (BAT) and the cutaneous vasculature. In anesthetized rats, pretreatment with indomethacin, a non-selective COX inhibitor, did not prevent BAT thermogenesis or cutaneous vasoconstriction (CVC) induced by intravenous IL-1β (2 µg/kg). BAT and cutaneous vasculature sympathetic premotor neurons in the rostral raphe pallidus area (rRPa) are required for IL-1β-evoked BAT thermogenesis and CVC, with or without pretreatment with indomethacin. Additionally, activation of glutamate receptors in the dorsomedial hypothalamus (DMH) is required for COX-independent, IL-1β-induced BAT thermogenesis. Therefore, our data suggests that COX-independent mechanisms elicit activation of neurons within the DMH and rRPa, which is sufficient to trigger and mount inflammatory fever. These data provide a foundation for elucidating the brain circuits responsible for COX-independent, IL-1β-elicited fevers.
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Affiliation(s)
| | - Christopher J. Madden
- Corresponding author at: Dept. of Neurological Surgery, Oregon Health & Science University, 3181 Sam Jackson Park Road, Portland, OR 97239, United States. (C.J. Madden)
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Co-Infections, Secondary Infections, and Antimicrobial Use in Patients Hospitalized with COVID-19 during the First Five Waves of the Pandemic in Pakistan; Findings and Implications. Antibiotics (Basel) 2022; 11:antibiotics11060789. [PMID: 35740195 PMCID: PMC9219883 DOI: 10.3390/antibiotics11060789] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Revised: 05/31/2022] [Accepted: 06/03/2022] [Indexed: 02/01/2023] Open
Abstract
Background: COVID-19 patients are typically prescribed antibiotics empirically despite concerns. There is a need to evaluate antibiotic use among hospitalized COVID-19 patients during successive pandemic waves in Pakistan alongside co-infection rates. Methods: A retrospective review of patient records among five tertiary care hospitals during successive waves was conducted. Data were collected from confirmed COVID-19 patients during the first five waves. Results: 3221 patients were included. The majority were male (51.53%), residents from urban areas (56.35%) and aged >50 years (52.06%). Cough, fever and a sore throat were the clinical symptoms in 20.39%, 12.97% and 9.50% of patients, respectively. A total of 23.62% of COVID-19 patients presented with typically mild disease and 45.48% presented with moderate disease. A high prevalence of antibiotic prescribing (89.69%), averaging 1.66 antibiotics per patient despite there only being 1.14% bacterial co-infections and 3.14% secondary infections, was found. Antibiotic use significantly increased with increasing severity, elevated WBCs and CRP levels, a need for oxygen and admittance to the ICU; however, this decreased significantly after the second wave (p < 0.001). Commonly prescribed antibiotics were piperacillin plus an enzyme inhibitor (20.66%), azithromycin (17.37%) and meropenem (15.45%). Common pathogens were Staphylococcus aureus (24.19%) and Streptococcus pneumoniae (20.96%). The majority of the prescribed antibiotics (93.35%) were from the WHO’s “Watch” category. Conclusions: Excessive prescribing of antibiotics is still occurring among COVID-19 patients in Pakistan; however, rates are reducing. Urgent measures are needed for further reductions.
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Tekale S, Gore V, Kendrekar P, Thore S, Kótai L, Pawar R. COVID-19 Global Pandemic Fight by Drugs: A Mini-Review on Hope and Hype. MINI-REV ORG CHEM 2022. [DOI: 10.2174/1570193x18666210629103117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
:
Coronavirus disease 2019 (Covid-19), a serious disease caused by the Severe Acute Respiratory
Syndrome-Corona Virus-2 (SARS-CoV-2), was firstly identified in the city of Wuhan of
China in December 2019, which then spread and became a global issue due to its high transmission
rate. To date, the outbreak of COVID-19 has resulted in infection to 230,868,745 people and the death
of 4,732,669 patients. It has paralyzed the economy of all the countries worldwide. Considering the
possible mutations of SARS-CoV-2, the current medical emergency requires a longer time for drug
design and vaccine development. Drug repurposing is a promising option for potent therapeutics
against the pandemic. The present review encompasses various drugs or appropriate combinations of
already FDA-approved antimalarial, antiviral, anticancer, anti-inflammatory, and antibiotic therapeutic
candidates for use in the clinical trials as a ray of hope against COVID-19. It is expected to deliver
better clinical and laboratory outcomes of drugs as a prevention strategy for the eradication of the disease.
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Affiliation(s)
- Sunil Tekale
- Department of Chemistry, Deogiri College, Aurangabad-431005, Maharashtra, India
| | - Vishnu Gore
- Department of Chemistry, Deogiri College, Aurangabad-431005, Maharashtra, India
| | - Pravin Kendrekar
- Unit for Drug Discovery Research (UDDR), Department of Health and Environmental Sciences, Central University of Technology, Free State (CUT) Private Bag X20539, Bloemfontein, 9300, South Africa
| | - Shivaji Thore
- Department of Chemistry, Deogiri College, Aurangabad-431005, Maharashtra, India
| | - László Kótai
- Research Centre for Natural Sciences, ELKH, H-1117, Budapest, Hungary
| | - Rajendra Pawar
- Department of Chemistry, Shiv Chhatrapati College, Cidco, Aurangabad-431005, Maharashtra, India
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Saraya RE, Deeb SE, Salman BI, Ibrahim AE. Highly sensitive high-performance thin-layer chromatography method for the simultaneous determination of Molnupiravir, Favipiravir, and Ritonavir in pure forms and pharmaceutical formulations. J Sep Sci 2022; 45:2582-2590. [PMID: 35583051 DOI: 10.1002/jssc.202200178] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 05/08/2022] [Accepted: 05/15/2022] [Indexed: 11/06/2022]
Abstract
Favipiravir, molnupiravir, and ritonavir have been recently approved as the first oral antivirals for treatment of SARS-CoV-2 viral infections. Their combination was reported in several clinical studies, alternatively, to enhance the viral eradication and improve patient's recovery times and rates. Being all orally administered, therefore, developing new sensitive and validated methodologies for their simultaneous determination is a necessitate. In the proposed research, a sensitive, selective and simple high-performance thin layer chromatography method was developed and validated for determination of favipiravir, molnupiravir, and ritonavir. Silica gel 60F254 thin layer chromatography plates were used as stationary phase for this separation using mobile phase composed of methylene chloride: ethyl acetate: methanol: 25% ammonia (6:3:4:1, v/v/v/v). Densitometric detection was performed at wavelength 289nm. Peaks of favipiravir, molnupiravir, and ritonavir were resolved at retention factors 0.22, 0.42 and 0.63, respectively. The proposed method was found linear within the specified ranges of 3.75-100.00 μg/mL for molnupiravir and favipiravir, and 2.75-100.00 μg/mL for ritonavir. Limits of detection were found to be 1.12, 1.21, and 0.89 μg/mL for favipiravir, molnupiravir, and ritonavir, respectively. This is the first method to be reported for the simultaneous determination of the cited three antiviral drugs. The method was assessed on novel greenness metrics. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Roshdy E Saraya
- Pharmaceutical analytical chemistry department, Faculty of Pharmacy, Port-Said University, Port-Said, Egypt
| | - Sami El Deeb
- Institute of Medicinal and Pharmaceutical Chemistry, Technische Universitaet Braunschweig, 38106, Braunschweig, Germany.,Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, Birkat Al Mauz, Nizwa, 616, Sultanate of Oman
| | - Baher I Salman
- Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Assiut branch, Assiut, 71524, Egypt
| | - Adel Ehab Ibrahim
- Pharmaceutical analytical chemistry department, Faculty of Pharmacy, Port-Said University, Port-Said, Egypt.,Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, Birkat Al Mauz, Nizwa, 616, Sultanate of Oman
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Lan SH, Lai CC, Chang SP, Lu LC, Hung SH, Lin WT. Favipiravir-based treatment for outcomes of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials. Expert Rev Clin Pharmacol 2022; 15:759-766. [PMID: 35579014 DOI: 10.1080/17512433.2022.2078701] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND This meta-analysis of randomized controlled trials (RCTs) investigated the clinical efficacy and safety of favipiravir for patients with mild-to-critical COVID-19. METHODS PubMed, Web of Science, Ovid Medline, Embase, and Cochrane Central Register of Controlled Trials were searched for RCTs published before October 30, 2021. Only RCTs that compared the clinical efficacy and safety of favipiravir -based antiviral regimens (study group) with other alternative treatments or placebos (control group) in patients with COVID-19 were included. RESULTS Overall, the clinical improvement rate was significantly higher in the study group than in the control group at the assessment conducted after 14 days (OR, 1.83; 95% CI, 1.12-2.98). The rate of virological eradication was significantly higher in the study group than in the control group at the assessment conducted after 28 days (OR, 2.09; 95% CI, 1.15-3.78). No significant difference was observed in the rates of invasive mechanical ventilation requirement or ICU admission, mortality, or risk of an adverse event between the study and control groups. CONCLUSIONS Except the clinical improvement rate within 14 days and the virological eradication rate within 28 days, favipiravir-based treatment did not provide significantly additional benefit for patients with COVID-19. Therefore, more evidence is necessary.
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Affiliation(s)
- Shao-Huan Lan
- School of Pharmaceutical Sciences and Medical Technology, Putian University, Putian, 351100, China
| | - Chih-Cheng Lai
- Department of Internal Medicine, Kaohsiung Veterans General Hospital, Tainan Branch, Tainan, Taiwan
| | | | - Li-Chin Lu
- School of Management, Putian University, Putian, 351100, China
| | - Shun-Hsing Hung
- Division of Urology, Department of Surgery, Chi-Mei Hospital, Chia Li, Tainan, Taiwan
| | - Wei-Ting Lin
- Department of Orthopedic, Chi Mei Medical Center, Tainan, 71004, Taiwan
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Scavone C, Mascolo A, Rafaniello C, Sportiello L, Trama U, Zoccoli A, Bernardi FF, Racagni G, Berrino L, Castaldo G, Coscioni E, Rossi F, Capuano A. Therapeutic strategies to fight COVID-19: Which is the status artis? Br J Pharmacol 2022; 179:2128-2148. [PMID: 33960398 PMCID: PMC8239658 DOI: 10.1111/bph.15452] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 03/02/2021] [Accepted: 03/05/2021] [Indexed: 02/06/2023] Open
Abstract
COVID-19 is a complex disease, and many difficulties are faced today especially in the proper choice of pharmacological treatments. The role of antiviral agents for COVID-19 is still being investigated and evidence for immunomodulatory and anti-inflammatory drugs is quite conflicting, whereas the use of corticosteroids is supported by robust evidence. The use of heparins in hospitalized critically ill patients is preferred over other anticoagulants. There are conflicting data on the use of convalescent plasma and vitamin D. According to the World Health Organization (WHO), many vaccines are in Phase III clinical trials, and some of them have already received marketing approval in European countries and in the United States. In conclusion, drug repurposing has represented the main approach recently used in the treatment of patients with COVID-19. At this moment, analysis of efficacy and safety data of drugs and vaccines used in real-life context is strongly needed. LINKED ARTICLES: This article is part of a themed issue on The second wave: are we any closer to efficacious pharmacotherapy for COVID 19? (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.10/issuetoc.
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Affiliation(s)
- Cristina Scavone
- Department of Experimental MedicineUniversità degli studi della Campania ‘Luigi Vanvitelli’NaplesItaly
| | - Annamaria Mascolo
- Department of Experimental MedicineUniversità degli studi della Campania ‘Luigi Vanvitelli’NaplesItaly
| | - Concetta Rafaniello
- Department of Experimental MedicineUniversità degli studi della Campania ‘Luigi Vanvitelli’NaplesItaly
| | - Liberata Sportiello
- Department of Experimental MedicineUniversità degli studi della Campania ‘Luigi Vanvitelli’NaplesItaly
| | - Ugo Trama
- Regional Pharmaceutical UnitU.O.D. 06 Politica del Farmaco e DispositiviNaplesItaly
| | - Alice Zoccoli
- Clinical Innovation OfficeUniversità Campus Bio‐MedicoRomeItaly
| | - Francesca Futura Bernardi
- Department of Experimental MedicineUniversità degli studi della Campania ‘Luigi Vanvitelli’NaplesItaly
- Regional Pharmaceutical UnitU.O.D. 06 Politica del Farmaco e DispositiviNaplesItaly
| | - Giorgio Racagni
- Department of Pharmacological and Biomolecular SciencesUniversity of MilanMilanItaly
| | - Liberato Berrino
- Department of Experimental MedicineUniversità degli studi della Campania ‘Luigi Vanvitelli’NaplesItaly
| | - Giuseppe Castaldo
- Department of Molecular Medicine and Medical BiotechnologyUniversity of Napoli Federico IINaplesItaly
- CEINGE—Advanced Biotechnology ScarlNaplesItaly
| | | | - Francesco Rossi
- Department of Experimental MedicineUniversità degli studi della Campania ‘Luigi Vanvitelli’NaplesItaly
- Clinical Innovation OfficeUniversità Campus Bio‐MedicoRomeItaly
| | - Annalisa Capuano
- Department of Experimental MedicineUniversità degli studi della Campania ‘Luigi Vanvitelli’NaplesItaly
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Devi J, Kumar B, Taxak B. Recent advancements of organotin(IV) complexes derived from hydrazone and thiosemicarbazone ligands as potential anticancer agents. INORG CHEM COMMUN 2022. [DOI: 10.1016/j.inoche.2022.109208] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Sharaf YA, El Deeb S, Ibrahim AE, Al-Harrasi A, Sayed RA. Two Green Micellar HPLC and Mathematically Assisted UV Spectroscopic Methods for the Simultaneous Determination of Molnupiravir and Favipiravir as a Novel Combined COVID-19 Antiviral Regimen. Molecules 2022; 27:2330. [PMID: 35408729 PMCID: PMC9000667 DOI: 10.3390/molecules27072330] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 04/01/2022] [Accepted: 04/01/2022] [Indexed: 12/17/2022] Open
Abstract
Following the spread of the COVID-19 pandemic crisis, a race was initiated to find a successful regimen for postinfections. Among those trials, a recent study declared the efficacy of an antiviral combination of favipiravir (FAV) and molnupiravir (MLP). The combined regimen helped in a successful 60% eradication of the SARS-CoV-2 virus from the lungs of studied hamster models. Moreover, it prevented viral transmission to cohosted sentinels. Because both medications are orally bioavailable, the coformulation of FAV and MLP can be predicted. The developed study is aimed at developing new green and simple methods for the simultaneous determination of FAV and MLP and then at their application in the study of their dissolution behavior if coformulated together. A green micellar HPLC method was validated using an RP-C18 core-shell column (5 μm, 150 × 4.6 mm) and an isocratic mixed micellar mobile phase composed of 0.1 M SDS, 0.01 M Brij-35, and 0.02 M monobasic potassium phosphate mixture and adjusted to pH 3.1 at 1.0 mL min-1 flow rate. The analytes were detected at 230 nm. The run time was less than five minutes under the optimized chromatographic conditions. Four other multivariate chemometric model methods were developed and validated, namely, classical least square (CLS), principal component regression (PCR), partial least squares (PLS-1), and genetic algorithm-partial least squares (GA-PLS-1). The developed models succeeded in resolving the great similarity and overlapping in the FAV and MLP UV spectra unlike the traditional univariate methods. All methods were organic solvent-free, did not require extraction or derivatization steps, and were applied for the construction of the simultaneous dissolution profile for FAV tablets and MLP capsules. The methods revealed that the amount of the simultaneously released cited drugs increases up until reaching a plateau after 15 and 20 min for FAV and MLP, respectively. The greenness was assessed on GAPI and found to be in harmony with green analytical chemistry concepts.
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Affiliation(s)
- Yasmine Ahmed Sharaf
- Analytical Chemistry Department, Faculty of Pharmacy, Zagazig University, Zagazig 44511, Egypt; (Y.A.S.); (R.A.S.)
| | - Sami El Deeb
- Institute of Medicinal and Pharmaceutical Chemistry, Technische Universitaet Braunschweig, 38106 Braunschweig, Germany
- Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, Birkat Al Mauz, Nizwa 616, Oman; (A.E.I.); (A.A.-H.)
| | - Adel Ehab Ibrahim
- Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, Birkat Al Mauz, Nizwa 616, Oman; (A.E.I.); (A.A.-H.)
- Analytical Chemistry Department, Faculty of Pharmacy, Port-Said University, Port Said 42526, Egypt
| | - Ahmed Al-Harrasi
- Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, Birkat Al Mauz, Nizwa 616, Oman; (A.E.I.); (A.A.-H.)
| | - Rania Adel Sayed
- Analytical Chemistry Department, Faculty of Pharmacy, Zagazig University, Zagazig 44511, Egypt; (Y.A.S.); (R.A.S.)
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Nair R, Soni M, Bajpai B, Dhiman G, Sagayam KM. Predicting the Death Rate Around the World Due to COVID-19 Using Regression Analysis. INTERNATIONAL JOURNAL OF SWARM INTELLIGENCE RESEARCH 2022. [DOI: 10.4018/ijsir.287545] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Nowadays, COVID-19 is considered to be the biggest disaster that the world is facing. It has created a lot of destruction in the whole world. Due to this COVID-19, analysis has been done to predict the death rate and infected rate from the total population. To perform the analysis on COVID-19, regression analysis has been implemented by applying the differential equation and ordinary differential equation (ODE) on the parameters. The parameters taken for analysis are the number of susceptible individuals, the number of Infected Individuals, and the number of Recovered Individuals. This work will predict the total cases, death cases, and infected cases in the near future based on different reproductive rate values. This work has shown the comparison based on 4 different productive rates i.e. 2.45, 2.55, 2.65, and 2.75. The analysis is done on two different datasets; the first dataset is related to China, and the second dataset is associated with the world's data. The work has predicted that by 2020-08-12: 59,450,123 new cases and 432,499,003 total cases and 10,928,383 deaths.
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Badavath VN, Kumar A, Samanta PK, Maji S, Das A, Blum G, Jha A, Sen A. Determination of potential inhibitors based on isatin derivatives against SARS-CoV-2 main protease (m pro): a molecular docking, molecular dynamics and structure-activity relationship studies. J Biomol Struct Dyn 2022; 40:3110-3128. [PMID: 33200681 PMCID: PMC7682386 DOI: 10.1080/07391102.2020.1845800] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Accepted: 10/29/2020] [Indexed: 12/27/2022]
Abstract
SARS-COV-2, the novel coronavirus and root of global pandemic COVID-19 caused a severe health threat throughout the world. Lack of specific treatments raised an effort to find potential inhibitors for the viral proteins. The recently invented crystal structure of SARS-CoV-2 main protease (Mpro) and its key role in viral replication; non-resemblance to any human protease makes it a perfect target for inhibitor research. This article reports a computer-aided drug design (CADD) approach for the screening of 118 compounds with 16 distinct heterocyclic moieties in comparison with 5 natural products and 7 repurposed drugs. Molecular docking analysis against Mpro protein were performed finding isatin linked with a oxidiazoles (A2 and A4) derivatives to have the best docking scores of -11.22 kcal/mol and -11.15 kcal/mol respectively. Structure-activity relationship studies showed a good comparison with a known active Mpro inhibitor and repurposed drug ebselen with an IC50 value of -0.67 μM. Molecular Dynamics (MD) simulations for 50 ns were performed for A2 and A4 supporting the stability of the two compounds within the binding pocket, largely at the S1, S2 and S4 domains with high binding energy suggesting their suitability as potential inhibitors of Mpro for SARS-CoV-2.
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Affiliation(s)
| | - Akhil Kumar
- Biotechnology Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, India
| | - Pralok K. Samanta
- School of Chemical and Bioprocess Engineering, University College Dublin, Dublin, Ireland
| | - Siddhartha Maji
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, India
| | - Anik Das
- Department of Chemistry, Institute of Science, GITAM (Deemed to be University), Visakhapatnam, India
| | - Galia Blum
- Institute for Drug Research, The Hebrew University, Jerusalem, Israel
| | - Anjali Jha
- Department of Chemistry, Institute of Science, GITAM (Deemed to be University), Visakhapatnam, India
| | - Anik Sen
- Department of Chemistry, Institute of Science, GITAM (Deemed to be University), Visakhapatnam, India
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