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Alric L, Brusq C, Migueres M, Faure S, Lebray P, Viallard JF, Chauveau D, Sailler L, Bérard E, Pugnet G, Cacoub P. Evaluation of the effects of pre-exposure treatment with hydroxychloroquine on the risk of COVID-19 infection and on the efficacy of anti-COVID-19 vaccination during lupus or Gougerot-Sjögren's disease: Prepcov multicentre trial. Lupus Sci Med 2025; 12:e001435. [PMID: 40044500 PMCID: PMC11883547 DOI: 10.1136/lupus-2024-001435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 02/21/2025] [Indexed: 03/09/2025]
Abstract
OBJECTIVES Some patients with SLE or Gougerot-Sjögren's disease (GSD) receive long-term treatment with hydroxychloroquine (HCQ), sometimes combined with immunosuppressive therapy (IS). This study sought to assess whether long-term HCQ therapy that had been initiated long before the COVID-19 pandemic had a protective or adverse effect on COVID-19 risk, severity of infection or immunity protection. METHODS This prospective multicentre study included 547 patients with SLE, GSD, autoimmune hepatitis, primary biliary cholangitis or cured viral hepatitis C divided into four groups according to HCQ (+/-) and IS (+/-) intake prior to the pandemic: HCQ+IS+ (n=112), HCQ+IS- (n=121), HCQ-IS+ (n=115) and HCQ-IS- (n=199). When COVID-19 vaccination was possible, patients were vaccinated as recommended. Vaccination efficacy was prospectively assessed on the basis of the postvaccination antibody titre. RESULTS Compared with HCQ+IS+ patients, HCQ-IS+ patients had a decreased risk of COVID-19 infection (p<0.001). Compared with HCQ+IS+ patients, HCQ-IS- patients had a decreased risk of contracting COVID-19 (p<0.001). Patients in the HCQ-IS+ or HCQ-IS- group had a lower risk of symptomatic or severe infection than HCQ+IS+ patients did (p=0.001 and p<0.001, respectively). Only patients who had two or more exposures (to vaccine and/or infection) had an increased likelihood of COVID-19 immunity after the last dose (p<0.001). CONCLUSIONS HCQ treatment that was initiated before the pandemic did not protect against COVID-19 infection. Moreover, non-exposure to HCQ treatment (combined or not with IS) was associated with decreased risk of COVID-19 infection and of developing a symptomatic or severe infection. HCQ and IS do not influence the vaccine response. Only two or more doses of vaccine result in a good vaccine response. TRIAL REGISTRATION NUMBER NCT04481633.
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Affiliation(s)
- Laurent Alric
- Toulouse III University-Paul Sabatier, Toulouse, France
| | - Clara Brusq
- Unité de Soutien Méthodologique à la Recherche (USMR), Service d'Epidémiologie Clinique et de Santé Publique, CHU de Toulouse, Toulouse III University-Paul Sabatier, Toulouse, France
| | | | - Stephanie Faure
- Hepatogastroenterology, Montpellier University, Montpellier, France
| | - Pascal Lebray
- Hepatology Unit, Hopital Universitaire Pitie-Salpetriere, Paris, France
| | | | - Dominique Chauveau
- Kidney Disease Unit, Toulouse III University-Paul Sabatier Faculty of Health, Toulouse, France
| | | | - Emilie Bérard
- Service d'Epidémiologie et Santé Publique, Toulouse III University-Paul Sabatier Faculty of Health, Toulouse, France
| | - Grégory Pugnet
- Internal Medicine Department, Toulouse III University-Paul Sabatier Faculty of Health, Toulouse, France
| | - Patrice Cacoub
- Service de Médecine Interne et Immunologie Clinique, Hopital Pitie-Salpetriere, Paris, France
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Sansone NMS, Boschiero MN, Marson FAL. Efficacy of Ivermectin, Chloroquine/Hydroxychloroquine, and Azithromycin in Managing COVID-19: A Systematic Review of Phase III Clinical Trials. Biomedicines 2024; 12:2206. [PMID: 39457519 PMCID: PMC11505156 DOI: 10.3390/biomedicines12102206] [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: 08/23/2024] [Revised: 09/18/2024] [Accepted: 09/21/2024] [Indexed: 10/28/2024] Open
Abstract
Background: During the coronavirus disease (COVID)-19 pandemic several drugs were used to manage the patients mainly those with a severe phenotype. Potential drugs were used off-label and major concerns arose from their applicability to managing the health crisis highlighting the importance of clinical trials. In this context, we described the mechanisms of the three repurposed drugs [Ivermectin-antiparasitic drug, Chloroquine/Hydroxychloroquine-antimalarial drugs, and Azithromycin-antimicrobial drug]; and, based on this description, the study evaluated the clinical efficacy of those drugs published in clinical trials. The use of these drugs reflects the period of uncertainty that marked the beginning of the COVID-19 pandemic, which made them a possible treatment for COVID-19. Methods: In our review, we evaluated phase III randomized controlled clinical trials (RCTs) that analyzed the efficacy of these drugs published from the COVID-19 pandemic onset to 2023. We included eight RCTs published for Ivermectin, 11 RCTs for Chloroquine/Hydroxychloroquine, and three RCTs for Azithromycin. The research question (PICOT) accounted for P-hospitalized patients with confirmed or suspected COVID-19; I-use of oral or intravenous Ivermectin OR Chloroquine/Hydroxychloroquine OR Azithromycin; C-placebo or no placebo (standard of care); O-mortality OR hospitalization OR viral clearance OR need for mechanical ventilation OR clinical improvement; and T-phase III RCTs. Results: While studying these drugs' respective mechanisms of action, the reasons for which they were thought to be useful became apparent and are as follows: Ivermectin binds to insulin-like growth factor and prevents nuclear transportation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), therefore preventing cell entrance, induces apoptosis, and osmotic cell death and disrupts viral replication. Chloroquine/Hydroxychloroquine blocks the movement of SARS-CoV-2 from early endosomes to lysosomes inside the cell, also, this drug blocks the binding between SARS-CoV-2 and Angiotensin-Converting Enzyme (ACE)-2 inhibiting the interaction between the virus spike proteins and the cell membrane and this drug can also inhibit SARS-CoV-2 viral replication causing, ultimately, the reduction in viral infection as well as the potential to progression for a higher severity phenotype culminating with a higher chance of death. Azithromycin exerts a down-regulating effect on the inflammatory cascade, attenuating the excessive production of cytokines and inducing phagocytic activity, and acts interfering with the viral replication cycle. Ivermectin, when compared to standard care or placebo, did not reduce the disease severity, need for mechanical ventilation, need for intensive care unit, or in-hospital mortality. Only one study demonstrated that Ivermectin may improve viral clearance compared to placebo. Individuals who received Chloroquine/Hydroxychloroquine did not present a lower incidence of death, improved clinical status, or higher chance of respiratory deterioration compared to those who received usual care or placebo. Also, some studies demonstrated that Chloroquine/Hydroxychloroquine resulted in worse outcomes and side-effects included severe ones. Adding Azithromycin to a standard of care did not result in clinical improvement in hospitalized COVID-19 participants. In brief, COVID-19 was one of the deadliest pandemics in modern human history. Due to the potential health catastrophe caused by SARS-CoV-2, a global effort was made to evaluate treatments for COVID-19 to attenuate its impact on the human species. Unfortunately, several countries prematurely justified the emergency use of drugs that showed only in vitro effects against SARS-CoV-2, with a dearth of evidence supporting efficacy in humans. In this context, we reviewed the mechanisms of several drugs proposed to treat COVID-19, including Ivermectin, Chloroquine/Hydroxychloroquine, and Azithromycin, as well as the phase III clinical trials that evaluated the efficacy of these drugs for treating patients with this respiratory disease. Conclusions: As the main finding, although Ivermectin, Chloroquine/Hydroxychloroquine, and Azithromycin might have mechanistic effects against SARS-CoV-2 infection, most phase III clinical trials observed no treatment benefit in patients with COVID-19, underscoring the need for robust phase III clinical trials.
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Affiliation(s)
- Nathália Mariana Santos Sansone
- Laboratory of Molecular Biology and Genetics, Laboratory of Clinical and Molecular Microbiology, LunGuardian Research Group—Epidemiology of Respiratory and Infectious Diseases, São Francisco University, Bragança Paulista 12916-900, SP, Brazil; (N.M.S.S.); (M.N.B.)
| | - Matheus Negri Boschiero
- Laboratory of Molecular Biology and Genetics, Laboratory of Clinical and Molecular Microbiology, LunGuardian Research Group—Epidemiology of Respiratory and Infectious Diseases, São Francisco University, Bragança Paulista 12916-900, SP, Brazil; (N.M.S.S.); (M.N.B.)
- São Paulo Hospital, Federal University of São Paulo, São Paulo 04023-062, SP, Brazil
| | - Fernando Augusto Lima Marson
- Laboratory of Molecular Biology and Genetics, Laboratory of Clinical and Molecular Microbiology, LunGuardian Research Group—Epidemiology of Respiratory and Infectious Diseases, São Francisco University, Bragança Paulista 12916-900, SP, Brazil; (N.M.S.S.); (M.N.B.)
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Abisheva S, Rutskaya-Moroshan K, Nuranova G, Batyrkhan T, Abisheva A. Antimalarial Drugs at the Intersection of SARS-CoV-2 and Rheumatic Diseases: What Are the Potential Opportunities? MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1171. [PMID: 39064600 PMCID: PMC11279047 DOI: 10.3390/medicina60071171] [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: 05/29/2024] [Revised: 07/14/2024] [Accepted: 07/15/2024] [Indexed: 07/28/2024]
Abstract
Background and Objectives: The coronavirus disease of 2019 (COVID-19) pandemic has posed a serious threat to humanity and is considered a global health emergency. Antimalarial drugs (ADs) have been used in the treatment of immuno-inflammatory arthritis (IIA) and coronavirus infection (COVID-19). The aim of this review is to analyze the current knowledge about the immunomodulatory and antiviral mechanisms of action, characteristics of use, and side effects of antimalarial drugs. Material and Methods: A literature search was carried out using PubMed, MEDLINE, SCOPUS, and Google Scholar databases. The inclusion criteria were the results of randomized and cohort studies, meta-analyses, systematic reviews, and original full-text manuscripts in the English language containing statistically confirmed conclusions. The exclusion criteria were summary reports, newspaper articles, and personal messages. Qualitative methods were used for theoretical knowledge on antimalarial drug usage in AIRDs and SARS-CoV-2 such as a summarization of the literature and a comparison of the treatment methods. Results: The ADs were considered a "candidate" for the therapy of a new coronavirus infection due to mechanisms of antiviral activity, such as interactions with endocytic pathways, the prevention of glycosylation of the ACE2 receptors, blocking sialic acid receptors, and reducing the manifestations of cytokine storms. The majority of clinical trials suggest no role of antimalarial drugs in COVID-19 treatment or prevention. These circumstances do not allow for their use in the treatment and prevention of COVID-19. Conclusions: The mechanisms of hydroxychloroquine are related to potential cardiotoxic manifestations and demonstrate potential adverse effects when used for COVID-19. Furthermore, the need for high doses in the treatment of viral infections increases the likelihood of gastrointestinal side effects, the prolongation of QT, and retinopathy. Large randomized clinical trials (RCTs) have refuted the fact that there is a positive effect on the course and results of COVID-19.
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Affiliation(s)
- Saule Abisheva
- Department of Family Medicine №1, NJSC “Astana Medical University”, Astana 010000, Kazakhstan; (S.A.); (T.B.); (A.A.)
| | - Kristina Rutskaya-Moroshan
- Department of Family Medicine №1, NJSC “Astana Medical University”, Astana 010000, Kazakhstan; (S.A.); (T.B.); (A.A.)
| | - Gulnaz Nuranova
- Department of Children’s Diseases with Courses in Pulmonology and Nephrology, NJSC “Astana Medical University”, Astana 010000, Kazakhstan;
| | - Tansholpan Batyrkhan
- Department of Family Medicine №1, NJSC “Astana Medical University”, Astana 010000, Kazakhstan; (S.A.); (T.B.); (A.A.)
| | - Anilim Abisheva
- Department of Family Medicine №1, NJSC “Astana Medical University”, Astana 010000, Kazakhstan; (S.A.); (T.B.); (A.A.)
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Ercan G, Saylav Bora E, Çınaroğlu OS, Karaali R, Erbas O. Hydroxychloroquine attenuates sepsis-induced acute respiratory distress syndrome in rats. ULUS TRAVMA ACIL CER 2024; 30:465-471. [PMID: 38967533 PMCID: PMC11331349 DOI: 10.14744/tjtes.2024.98855] [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: 03/16/2024] [Revised: 03/27/2024] [Accepted: 06/04/2024] [Indexed: 07/06/2024]
Abstract
BACKGROUND This study investigates the effects of hydroxychloroquine (HCQ) on a sepsis-induced acute respiratory distress syndrome (ARDS) model in rats, initiated by a fecal intraperitoneal injection procedure (FIP). METHODS Three groups were established: control (n=8), FIP + saline (n=7), and FIP + HCQ (20 mg/kg/day) (n=9). Blood samples were collected for arterial blood gas and biochemical analyses, and bilateral pneumonectomy was performed for histopathologic examination. RESULTS In the FIP + saline group, PaO2 decreased and PaCO2 increased, whereas these levels normalized in the FIP + HCQ group compared to the control (p<0.001 and p<0.05, respectively). Histopathological scores for alveolar congestion, perivascular/interstitial edema, hemorrhage in alveolar tissue, leukocyte infiltration or aggregation in air spaces/vascular walls, and alveolar wall/hyaline membrane thickness increased in the FIP + saline group compared to the control group (p<0.01). These scores decreased in the FIP + HCQ group compared to the FIP + saline group (p<0.01). HCQ reversed the sepsis-induced increase in malondialdehyde, tumor necrosis factor-alpha, interleukin-6, and lactic acid. CONCLUSION HCQ may be an effective and safe option to mitigate the severe progression of ARDS.
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Affiliation(s)
- Gulcin Ercan
- Department of General Surgery, Sultan 2. Abdulhamid Han Educational and Research Hospital, Istanbul Provincial Directorate of Health, Istanbul-Türkiye
| | - Ejder Saylav Bora
- Department of Emergency Medicine, Izmir Katip Çelebi University Faculty of Medicine, Izmir-Türkiye
| | - Osman Sezer Çınaroğlu
- Department of Emergency Medicine, Izmir Katip Çelebi University Faculty of Medicine, Izmir-Türkiye
| | - Rezan Karaali
- Department of Emergency Medicine, Izmir Demokrasi University Faculty of Medicine, Izmir-Türkiye
| | - Oytun Erbas
- Department of Physiology, Demiroğlu University Faculty of Medicine, İstanbul-Türkiye
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Han X, Shi W, Yang Y. The efficacy and safety of hydroxychloroquine for COVID-19 prophylaxis and clinical assessment: an updated meta-analysis of randomized trials. J Thorac Dis 2024; 16:2983-2993. [PMID: 38883686 PMCID: PMC11170382 DOI: 10.21037/jtd-23-1043] [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: 07/06/2023] [Accepted: 03/29/2024] [Indexed: 06/18/2024]
Abstract
Background Coronavirus disease 2019 (COVID-19), a disease that affected tens of millions of people, upended the lives of countless individuals around the globe. The chloroquine (CQ) and its analogue hydroxychloroquine (HCQ) were the most frequently cited as potential treatments and preventatives against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The primary aim of this investigation was to scrutinize the effectiveness and safety of HCQ for COVID-19 prevention and to present powerful evidence and reference for clinical practice. Methods PubMed, Ovid and the Cochrane COVID-19 Register of Controlled Trials (CENTRAL) were systematically searched from inception to January 31, 2022. Randomized controlled trials (RCTs) trials that included participants who were SARS-CoV-2 negative at the time of registration were enrolled in this meta-analysis. The intervention group took HCQ or CQ orally. The control group was not blinded by quinine or placebo. Pooled relative risk (RR) of SARS-CoV-2 infection, mortality, hospitalization, adverse events, and compliance were calculated. The software tools utilized for statistical analyses were Stata 14 and Review Manager 5.3. Results A total of 9 studies including 7,825 participants were enrolled. Bias of individual studies were assessed as low risk. The pooled RR for SARS-CoV-2 infection was 0.75 [95% confidence interval (CI): 0.68-0.83] (z=-4.01, P<0.0001; I2=11%). The pooled RR for hospitalization was 0.72 (95% CI: 0.35-1.50) (z=0.87, P=0.39; I2=0.0%). The pooled RR for mortality and adverse events were 3.26 (95% CI: 0.13-79.74) (z=0.72, P=0.47; I2=0.0%) and 1.90 (95% CI: 1.20-3.02) (z=2.73, P=0.0063; I2=94%). Conclusions Results of this meta-analysis indicated significant impact of HCQ on SARS-CoV-2 infection with higher risk of adverse events. These findings must be considered with caution, and further research is necessary to delineate the specific circumstances where HCQ may be effective for COVID-19 prevention.
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Affiliation(s)
- Xudong Han
- Nursing Department, Dahua Hospital, Xuhui District, Shanghai, China
| | - Wei Shi
- Nursing Department, Dahua Hospital, Xuhui District, Shanghai, China
| | - Ya Yang
- Nursing Department, Dahua Hospital, Xuhui District, Shanghai, China
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Zhao X, Wu H, Li S, Gao C, Wang J, Ge L, Song Z, Ni B, You Y. The impact of the COVID-19 pandemic on SLE. Mod Rheumatol 2024; 34:247-264. [PMID: 36961736 DOI: 10.1093/mr/road030] [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: 12/13/2022] [Revised: 02/21/2023] [Accepted: 03/11/2023] [Indexed: 03/25/2023]
Abstract
Little is known about the association between coronavirus disease 2019 (COVID-19) and autoimmune diseases, especially in the case of systemic lupus erythematosus (SLE). SLE patients met with many questions during the pandemic in COVID-19, such as how to minimize risk of infection, the complex pathological features and cytokine profiles, diagnosis and treatment, rational choice of drugs and vaccine, good nursing, psychological supervision, and so on. In this study, we review and discuss the multifaceted effects of the COVID-19 pandemic on patients living with SLE using the available literature. Cross-talk in implicated inflammatory pathways/mechanisms exists between SLE and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and SARS-CoV-2 displays similar clinical characteristics and immuno-inflammatory responses to SLE. Current epidemiological data inadequately assess the risk and severity of COVID-19 infection in patients with SLE. More evidence has shown that hydroxychloroquine and chloroquine cannot prevent COVID-19. During the pandemic, patients with SLE had a higher rate of hospitalization. Vaccination helps to reduce the risk of infection. Several therapies for patients with SLE infected with COVID-19 are discussed. The cases in the study can provide meaningful information for clinical diagnosis and management. Our main aim is to help preventing infection and highlight treatment options for patients with SLE infected with COVID-19.
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Affiliation(s)
- Xingwang Zhao
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Haohao Wu
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Shifei Li
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Cuie Gao
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Juan Wang
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Lan Ge
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Zhiqiang Song
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Bing Ni
- Department of Pathophysiology, College of High Altitude Military Medicine, Army Medical University (Third Military Medical University), Chongqing, China
| | - Yi You
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
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Panagiotides NG, Poledniczek M, Andreas M, Hülsmann M, Kocher AA, Kopp CW, Piechota-Polanczyk A, Weidenhammer A, Pavo N, Wadowski PP. Myocardial Oedema as a Consequence of Viral Infection and Persistence-A Narrative Review with Focus on COVID-19 and Post COVID Sequelae. Viruses 2024; 16:121. [PMID: 38257821 PMCID: PMC10818479 DOI: 10.3390/v16010121] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 01/02/2024] [Accepted: 01/09/2024] [Indexed: 01/24/2024] Open
Abstract
Microvascular integrity is a critical factor in myocardial fluid homeostasis. The subtle equilibrium between capillary filtration and lymphatic fluid removal is disturbed during pathological processes leading to inflammation, but also in hypoxia or due to alterations in vascular perfusion and coagulability. The degradation of the glycocalyx as the main component of the endothelial filtration barrier as well as pericyte disintegration results in the accumulation of interstitial and intracellular water. Moreover, lymphatic dysfunction evokes an increase in metabolic waste products, cytokines and inflammatory cells in the interstitial space contributing to myocardial oedema formation. This leads to myocardial stiffness and impaired contractility, eventually resulting in cardiomyocyte apoptosis, myocardial remodelling and fibrosis. The following article reviews pathophysiological inflammatory processes leading to myocardial oedema including myocarditis, ischaemia-reperfusion injury and viral infections with a special focus on the pathomechanisms evoked by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In addition, clinical implications including potential long-term effects due to viral persistence (long COVID), as well as treatment options, are discussed.
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Affiliation(s)
- Noel G. Panagiotides
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria; (N.G.P.); (M.P.); (M.H.); (A.W.); (N.P.)
| | - Michael Poledniczek
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria; (N.G.P.); (M.P.); (M.H.); (A.W.); (N.P.)
- Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria;
| | - Martin Andreas
- Department of Cardiac Surgery, Medical University of Vienna, 1090 Vienna, Austria; (M.A.); (A.A.K.)
| | - Martin Hülsmann
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria; (N.G.P.); (M.P.); (M.H.); (A.W.); (N.P.)
| | - Alfred A. Kocher
- Department of Cardiac Surgery, Medical University of Vienna, 1090 Vienna, Austria; (M.A.); (A.A.K.)
| | - Christoph W. Kopp
- Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria;
| | | | - Annika Weidenhammer
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria; (N.G.P.); (M.P.); (M.H.); (A.W.); (N.P.)
| | - Noemi Pavo
- Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria; (N.G.P.); (M.P.); (M.H.); (A.W.); (N.P.)
| | - Patricia P. Wadowski
- Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria;
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Gökalp F. An investigation into the usage of black cumin derivatives against cancer and COVID-19 as the nature medicine. J Biomol Struct Dyn 2024:1-8. [PMID: 38197611 DOI: 10.1080/07391102.2024.2302942] [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: 10/03/2023] [Accepted: 01/02/2024] [Indexed: 01/11/2024]
Abstract
Black cumin has been used as a spice and food preservative for years. Thymol, thymoquinone, thymohydroquinone and dihydrothymoquinone are the most important natural agents in black cumin. In order to determine the most active compound in black cumin the theoretical calculations have been carried out in different phases by using the density functional theory (DFT). The inhibition effect of black cumin derivatives on Histone deacetylase 2 (HDAC2) has been determined and supported the experimental studies without losing time and matter. The chemical activity, stability and solubility of the active substances in black cumin have been theoretically calculated. The chemical active compounds had been investigated in the black seeds when extracted with water. Their stability and polarity in blood and water are important parameters. HDAC2- dihydrothymoquinone interaction has been investigated. It has been determined that the active substances found in black cumin are very effective in protecting ACE2 against COVID-19 and by comparing the docking results of important receptors and selected ligands on COVID-19.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Faik Gökalp
- Department of Mathematics and Science Education, Education Faculty, Kırıkkale University, Yahşihan, Kırıkkale, Turkey
- Faculty of Health Sciences, Iğdır University, Iğdır, Turkey
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Heydari B, Sahebnasagh A, Omrani MA, Azimi S, Dehghani MH, Salehi-Abargouei A, Farman F, Saghafi F. Promises and Pitfalls of Calcineurin Inhibitors in COVID-19: A Systematic Review and Meta-analysis of Controlled Trials. Curr Med Chem 2024; 31:4745-4755. [PMID: 38099537 DOI: 10.2174/0109298673264362231022150520] [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: 05/27/2023] [Revised: 06/24/2023] [Accepted: 07/31/2023] [Indexed: 01/23/2025]
Abstract
OBJECTIVE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a violent attack on the body that leads to multi-organ failure and death in COVID-19 patients. The aim of this study was to systematically review the existing literature on the potential benefits of calcineurin inhibitors (CIs) as anti-vascular endothelial growth factor (VEGF) agents in improving the clinical outcomes of COVID-19 patients. METHODS We searched various databases, including PubMed, Scopus, ISI Web of Science, Google Scholar, Cochrane databases, and ClinicalTrials.gov from 31st December, 2019, to 3rd February, 2023, for relevant controlled trials. The quality of the evidence was assessed using the Cochrane Collaboration tool. Comprehensive Meta-Analysis Software was used for the statistical analyses using a random-effects model. RESULTS Three trials enrolling 293 participants were reviewed in the present systematic review and meta-analysis. The results showed CIs to lead to a significant reduction in mortality rate [risk ratio (RR): 0.598, 95% CI: 0.404-0.885, P-value = 0.010] with a low between-study heterogeneity (Cochrane Q test: I2 = 0.000%, P-value = 0.371). Pooled analysis of two studies (84 patients) illustrated that CIs could not significantly increase the rate of hospital discharge (RR: 1.161, 95% CI: 0.764-1.764, P-value = 0.485) and heterogeneity was not significant (Cochrane Q test: I2 = 26.798%, P-value = 0.242). CONCLUSION CIs are able to inhibit the virus nucleocapsid protein so that they can prevent replication and respiratory tract tissue damage caused by SARS-CoV-2. Based on the characteristics mentioned in detail, CIs can play a potential therapeutic role for COVID-19 patients.
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Affiliation(s)
- Behrooz Heydari
- Department of Clinical Pharmacy, School of Pharmacy, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
| | - Adeleh Sahebnasagh
- Department of Internal Medicine, Clinical Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Mohammad Ali Omrani
- Pharmaceutical Sciences Research Center, School of Pharmacy, Student Research Committee, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Saeed Azimi
- Student Research Committee, Department of Clinical Pharmacy, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Hossein Dehghani
- Department of Anesthesiology and Critical Care, Shahid Rahnemoun Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Amin Salehi-Abargouei
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Farnoosh Farman
- Pharmaceutical Sciences Research Center, School of Pharmacy, Student Research Committee, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Fatemeh Saghafi
- Department of Clinical Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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11
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Mia ME, Howlader M, Akter F, Hossain MM. Preclinical and Clinical Investigations of Potential Drugs and Vaccines for COVID-19 Therapy: A Comprehensive Review With Recent Update. CLINICAL PATHOLOGY (THOUSAND OAKS, VENTURA COUNTY, CALIF.) 2024; 17:2632010X241263054. [PMID: 39070952 PMCID: PMC11282570 DOI: 10.1177/2632010x241263054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Accepted: 06/03/2024] [Indexed: 07/30/2024]
Abstract
The COVID-19 pandemic-led worldwide healthcare crisis necessitates prompt societal, ecological, and medical efforts to stop or reduce the rising number of fatalities. Numerous mRNA based vaccines and vaccines for viral vectors have been licensed for use in emergencies which showed 90% to 95% efficacy in preventing SARS-CoV-2 infection. However, safety issues, vaccine reluctance, and skepticism remain major concerns for making mass vaccination a successful approach to treat COVID-19. Hence, alternative therapeutics is needed for eradicating the global burden of COVID-19 from developed and low-resource countries. Repurposing current medications and drug candidates could be a more viable option for treating SARS-CoV-2 as these therapies have previously passed a number of significant checkpoints for drug development and patient care. Besides vaccines, this review focused on the potential usage of alternative therapeutic agents including antiviral, antiparasitic, and antibacterial drugs, protease inhibitors, neuraminidase inhibitors, and monoclonal antibodies that are currently undergoing preclinical and clinical investigations to assess their effectiveness and safety in the treatment of COVID-19. Among the repurposed drugs, remdesivir is considered as the most promising agent, while favipiravir, molnupiravir, paxlovid, and lopinavir/ritonavir exhibited improved therapeutic effects in terms of elimination of viruses. However, the outcomes of treatment with oseltamivir, umifenovir, disulfiram, teicoplanin, and ivermectin were not significant. It is noteworthy that combining multiple drugs as therapy showcases impressive effectiveness in managing individuals with COVID-19. Tocilizumab is presently employed for the treatment of patients who exhibit COVID-19-related pneumonia. Numerous antiviral drugs such as galidesivir, griffithsin, and thapsigargin are under clinical trials which could be promising for treating COVID-19 individuals with severe symptoms. Supportive treatment for patients of COVID-19 may involve the use of corticosteroids, convalescent plasma, stem cells, pooled antibodies, vitamins, and natural substances. This study provides an updated progress in SARS-CoV-2 medications and a crucial guide for inventing novel interventions against COVID-19.
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Affiliation(s)
- Md. Easin Mia
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Mithu Howlader
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Farzana Akter
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Md. Murad Hossain
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh
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Al-Barzinji N, Jalal AM. Hydroxychloroquine-Induced Stevens-Johnson Syndrome in the Patient with Systemic Lupus Erythematosus: A Case Report in Kurdish Region - Iraq. Mediterr J Rheumatol 2023; 34:547-549. [PMID: 38282931 PMCID: PMC10815519 DOI: 10.31138/mjr.260723.his] [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: 11/02/2022] [Revised: 11/20/2022] [Accepted: 11/23/2022] [Indexed: 01/30/2024] Open
Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that mainly affects women. Hydroxychloroquine (HCQ) and chloroquine are widely used in the treatment of many diseases, such as malaria, rheumatic arthritis, systemic lupus erythematosus, and other Rheumatic diseases. The Stevens-Johnson Syndrome (SJS) is a rare immune complex-mediated hypersensitivity disorder that is characterised as a vesiculobullous erythema multiform of the skin, mouth, eyes, and genitals. We decided to report a thirty-year-old female patient with HCQ-developed side effects of induced SJS and its appropriate management. In conclusion, the HCQ tablet does have known side effects. One of the side effects of HCQ is SJS caused by the drug; given the worldwide use of this drug in Rheumatic diseases and its increasing need, we need to be careful about its use to control and manage its side effects.
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Ortiz-Prado E, Izquierdo-Condoy JS, Mora C, Vasconez-Gonzalez J, Fernandez-Naranjo R. Poor regulation, desperation, and misinformation, a countrywide analysis of self-medication and prescription patterns in Ecuador during the COVID-19 pandemic. Res Social Adm Pharm 2023; 19:1579-1589. [PMID: 37659922 DOI: 10.1016/j.sapharm.2023.08.011] [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: 02/13/2023] [Revised: 08/23/2023] [Accepted: 08/28/2023] [Indexed: 09/04/2023]
Abstract
BACKGROUND The rapid spread of the SARS-CoV-2 virus during the early phase of the pandemic led to an unprecedented global health crisis. Various factors have influenced self-medication practices among the general population and unsubstantiated prescribing practices among healthcare professionals. OBJECTIVE This study aimed to describe trends in the purchase and sale of medicines during the COVID-19 pandemic period (2020-2022) in Ecuador, by comparing them with pre-pandemic periods. METHODS In this study, a cross-sectional design was employed to conduct a comprehensive analysis of 28 pharmacological groups, categorized according to the Anatomical Therapeutic Chemical Classification (ATC). Utilizing an integrated drug consumption database, the study examined physician prescribing data, medicine usage, and spending levels in Ecuador during the COVID-19 pandemic. The analysis involved computing absolute differences in monthly resolution, calculating excessive expenditure in comparison to previous yearly averages, and using Defined Daily Dose (DDD) methodology for internationally comparable results. Furthermore, a correlation analysis was performed to investigate potential associations between prescribed and consumed medicines and the number of new cases and deaths. RESULTS In Ecuador, the average yearly expenditure among these groups prior to the pandemic (2017-2019) amounted to $150,646,206 USD, whereas during 2020 and 2021, the same groups represented a total expenditure of $228,327,210, reflecting a significant increase. The excess expenditure during this period reached 51.4%, equivalent to $77,681,004 USD. Notably, 13% of this expenditure consisted of Over the Counter (OTC) Medicines. The study also identified a remarkable surge in sales of ivermectin, which increased by 2,057%, and hydroxychloroquine, which increased by 171%, as measured by DDD. CONCLUSIONS This study highlights the substantial consumption of medicines by the population in Ecuador during the pandemic. It is concerning that many medications were sold without proven therapeutic indications, indicating that misinformation and desperation may have led to improper prescribing by physicians and patients resorting to ineffective drugs. Moreover, since the sale of these therapeutic drugs requires a prescription, poor regulation, and a lack of control within pharmacies likely contributed to such practices.
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Affiliation(s)
- Esteban Ortiz-Prado
- One Health Research Group, Faculty of Medicine, Universidad de Las Américas, Quito, 170125, Ecuador.
| | - Juan S Izquierdo-Condoy
- One Health Research Group, Faculty of Medicine, Universidad de Las Américas, Quito, 170125, Ecuador
| | - Carla Mora
- Medical Department, Quifatex, Quito, 170138, Ecuador
| | - Jorge Vasconez-Gonzalez
- One Health Research Group, Faculty of Medicine, Universidad de Las Américas, Quito, 170125, Ecuador
| | - Raúl Fernandez-Naranjo
- One Health Research Group, Faculty of Medicine, Universidad de Las Américas, Quito, 170125, Ecuador
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Aboul-Fotouh S, Mahmoud AN, Elnahas EM, Habib MZ, Abdelraouf SM. What are the current anti-COVID-19 drugs? From traditional to smart molecular mechanisms. Virol J 2023; 20:241. [PMID: 37875904 PMCID: PMC10594888 DOI: 10.1186/s12985-023-02210-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 10/13/2023] [Indexed: 10/26/2023] Open
Abstract
BACKGROUND Coronavirus disease 19 (COVID-19) is the disease caused by SARS-CoV-2, a highly infectious member of the coronavirus family, which emerged in December 2019 in "Wuhan, China". It induces respiratory illness ranging from mild symptoms to severe disease. It was declared a "pandemic" by the World Health Organization (WHO) in March 2020. Since then, a vast number of clinical and experimental studies have been conducted to identify effective approaches for its prevention and treatment. MAIN BODY The pathophysiology of COVID-19 represents an unprecedented challenge; it triggers a strong immune response, which may be exacerbated by "a cytokine storm syndrome". It also induces thrombogenesis and may trigger multi-organ injury. Therefore, different drug classes have been proposed for its treatment and prevention, such as antivirals, anti-SARS-CoV-2 antibody agents (monoclonal antibodies, convalescent plasma, and immunoglobulins), anti-inflammatory drugs, immunomodulators, and anticoagulant drugs. To the best of our knowledge, this review is the first to present, discuss, and summarize the current knowledge about the different drug classes used for the treatment of COVID-19, with special emphasis on their targets, mechanisms of action, and important adverse effects and drug interactions. Additionally, we spotlight the latest "October 2023" important guidelines (NIH, IDSA, and NICE) and FDA approval or authorization regarding the use of these agents in the management of COVID-19. CONCLUSION Despite the wide array of therapeutic strategies introduced for the treatment of COVID-19, one of the most prominent therapeutic challenges is SARS-CoV-2 mutations and emerging new variants and subvariants. Currently, the anti-COVID-19 drug pipeline is continuously affording novel treatments to face this growing challenge.
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Affiliation(s)
- Sawsan Aboul-Fotouh
- Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Clinical Pharmacology Unit, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Ahmed Nageh Mahmoud
- Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Esraa M Elnahas
- Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Z Habib
- Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
| | - Sahar M Abdelraouf
- Department of Biochemistry, Faculty of Pharmacy, Misr International University, Cairo, Egypt
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Chaudhary S, Joshi A, Sesham K, Rai P, Kumar S, Mridha AR, Baitha U, Nag TC, Yadav SC. Impact of prophylactic hydroxychloroquine on ultrastructural impairment and cellular SARS-CoV-2 infection in different cells of bronchoalveolar lavage fluids of COVID-19 patients. Sci Rep 2023; 13:12733. [PMID: 37543667 PMCID: PMC10404249 DOI: 10.1038/s41598-023-39941-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 08/02/2023] [Indexed: 08/07/2023] Open
Abstract
Many drugs were recommended as antiviral agents for infection control and effective therapy to reduce the mortality rate for COVID-19 patients. Hydroxychloroquine (HCQ), an antimalarial drug, has been controversially recommended for prophylactic use in many countries, including India, to control SARS-CoV-2 infections. We have explored the effect of prophylactic HCQ from the cells of bronchoalveolar lavage fluids from COVID-19-induced acute respiratory distress syndrome patients to determine the level of infection and ultrastructural alterations in the ciliated epithelium, type II pneumocytes, alveolar macrophages, neutrophils, and enucleated granulocytes. Ultrastructural investigation of ciliated epithelium and type II pneumocytes showed lesser infections and cellular impairment in the prophylactic HCQ+ group than HCQ- group. However, macrophages and neutrophils displayed similar infection and ultrastructural alterations in both patient groups. The enucleated fragments of granulocytes showed phagocytosis of the matured virus in HCQ+ groups. The present report unveils the ultrastructural proof to complement the paradox regarding the role of prophylactic HCQ in COVID-19 patients.
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Affiliation(s)
- Shikha Chaudhary
- Electron Microscope Facility, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, Delhi, 110029, India
| | - Arti Joshi
- Electron Microscope Facility, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, Delhi, 110029, India
| | - Kishore Sesham
- Electron Microscope Facility, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, Delhi, 110029, India
| | - Preeti Rai
- Electron Microscope Facility, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, Delhi, 110029, India
| | - Shailendra Kumar
- Department of Anaesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi, Delhi, 110029, India
| | - Asit Ranjan Mridha
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, Delhi, 110029, India
| | - Upendra Baitha
- Department of Medicine, All India Institute of Medical Sciences, New Delhi, Delhi, 110029, India
| | - Tapas Chandra Nag
- Electron Microscope Facility, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, Delhi, 110029, India
| | - Subhash Chandra Yadav
- Electron Microscope Facility, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, Delhi, 110029, India.
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Das S, Sharma T, Bhardwaj A, Srivastava RK. COVID-19 induced ARDS: immunopathology and therapeutics. EXPLORATION OF IMMUNOLOGY 2023:255-275. [DOI: 10.37349/ei.2023.00101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 06/14/2023] [Indexed: 01/03/2025]
Abstract
The coronavirus disease-2019 (COVID-19) pandemic is a significant threat in the modern era. Clinical studies show that the most common symptom of severe COVID-19 is viral pneumonia-induced acute respiratory distress syndrome (ARDS). The underlying mechanisms by which severe respiratory disease syndrome-coronavirus-2 (SARS-CoV-2) results in ARDS and how certain host factors confer an increased risk of developing severe disease remain unknown. Therefore, identifying the distinctive features of this severe and fatal disease and the therapeutic approaches to COVID-19-induced ARDS remains an immediate need to serve as a basis for best practice models of standardized ARDS treatment. This review article aims to comprehensively discuss the immunopathology of ARDS and provides an overview of the precise role of both the innate and adaptive immune system, with emphasis on the current treatment strategies being tested in the COVID-19-induced ARDS patients. This knowledge will supposedly help in revealing further mechanistic insights into understanding COVID-19-induced ARDS.
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Affiliation(s)
- Sneha Das
- Translational Immunology, Osteoimmunology & Immunoporosis Lab (TIOIL), Department of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India
| | - Tamanna Sharma
- Translational Immunology, Osteoimmunology & Immunoporosis Lab (TIOIL), Department of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India
| | - Asha Bhardwaj
- Translational Immunology, Osteoimmunology & Immunoporosis Lab (TIOIL), Department of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India
| | - Rupesh K. Srivastava
- Translational Immunology, Osteoimmunology & Immunoporosis Lab (TIOIL), Department of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India
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Yadiki J, Ali Alftaikhah SA. COVID-19 in third trimester of pregnancy. J Adv Pharm Technol Res 2023; 14:171-175. [PMID: 37692004 PMCID: PMC10483902 DOI: 10.4103/japtr.japtr_33_23] [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: 01/17/2023] [Revised: 04/20/2023] [Accepted: 06/01/2023] [Indexed: 09/12/2023] Open
Abstract
The COVID-19 pandemic disease, which affects the respiratory system and produces flu-like symptoms, is caused by the SARS-CoV-2 virus. It is transmitted by close contact, oronasal secretions, or droplets. In general, pregnant individuals are at increased risk than nonpregnant individuals for developing serious SARS-CoV-2 virus-related illnesses, particularly during the third trimester. Despite the lack of research on COVID-19-infected pregnant mothers, this review article has discussed the clinical and laboratory characteristics and impact of COVID-19 on delivery, management, and vaccination of pregnant individuals with COVID-19 infection.
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Affiliation(s)
- JosnaVinutha Yadiki
- Department of Preventive Dentistry, College of Dentistry, Jouf University, Sakaka, Aljouf Province, Saudi Arabia
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Bantun F. Fungal-Bacterial Co-Infections and Super-Infections among Hospitalized COVID-19 Patients: A Systematic Review. J Fungi (Basel) 2023; 9:598. [PMID: 37367534 PMCID: PMC10299597 DOI: 10.3390/jof9060598] [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: 02/11/2023] [Revised: 03/26/2023] [Accepted: 03/29/2023] [Indexed: 06/28/2023] Open
Abstract
This study systematically reviewed fungal-bacterial co-infections and super-infections among hospitalized COVID-19 patients. A PRISMA systematic search was conducted. On September 2022, Medline, PubMed, Google Scholar, PsychINFO, Wiley Online Library, NATURE, and CINAHL databases were searched for all relevant articles published in English. All articles that exclusively reported the presence of fungal-bacterial co-infections and super-infections among hospitalized COVID-19 patients were included. Seven databases produced 6937 articles as a result of the literature search. Twenty-four articles met the inclusion criteria and were included in the final analysis. The total number of samples across the studies was 10,834, with a total of 1243 (11.5%) patients admitted to the intensive care unit (ICU). Of these patients, 535 underwent mechanical ventilation (4.9%), 2386 (22.0%) were male, and 597 (5.5%) died. Furthermore, hospitalized COVID-19 patients have a somewhat high rate (23.5%) of fungal-bacterial co-infections and super-infections. Moreover, for SARS-CoV-2 patients who have a chest X-ray that suggests a bacterial infection, who require immediate ICU admission, or who have a seriously immunocompromised condition, empiric antibiotic therapy should be taken into consideration. Additionally, the prevalence of co-infections and super-infections among hospitalized COVID-19 patients may have an impact on diagnosis and treatment. It is crucial to check for fungal and bacterial co-infections and super-infections in COVID-19 patients.
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Affiliation(s)
- Farkad Bantun
- Department of Microbiology, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia
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19
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Khan MT, Shah IA, Hossain MF, Akther N, Zhou Y, Khan MS, Al-Shaeli M, Bacha MS, Ihsanullah I. Personal protective equipment (PPE) disposal during COVID-19: An emerging source of microplastic and microfiber pollution in the environment. THE SCIENCE OF THE TOTAL ENVIRONMENT 2023; 860:160322. [PMID: 36414071 PMCID: PMC9675081 DOI: 10.1016/j.scitotenv.2022.160322] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 11/13/2022] [Accepted: 11/16/2022] [Indexed: 05/29/2023]
Abstract
Waste generated by healthcare facilities during the COVID-19 pandemic has become a new source of pollution, particularly with the widespread use of single-use personal protective equipment (PPE). Releasing microplastics (MPs) and microfibers (MFs) from discarded PPE becomes an emerging threat to environmental sustainability. MPs/MFs have recently been reported in a variety of aquatic and terrestrial ecosystems, including water, deep-sea sediments, air, and soil. As COVID-19 spreads, the use of plastic-made PPE in healthcare facilities has increased significantly worldwide, resulting in massive amounts of plastic waste entering the terrestrial and marine environments. High loads of MPs/MFs emitted into the environment due to excessive PPE consumption are easily consumed by aquatic organisms, disrupting the food chain, and potentially causing chronic health problems in humans. Thus, proper management of PPE waste is critical for ensuring a post-COVID sustainable environment, which has recently attracted the attention of the scientific community. The current study aims to review the global consumption and sustainable management of discarded PPE in the context of COVID-19. The severe impacts of PPE-emitted MPs/MFs on human health and other environmental segments are briefly addressed. Despite extensive research progress in the area, many questions about MP/MF contamination in the context of COVID-19 remain unanswered. Therefore, in response to the post-COVID environmental remediation concerns, future research directions and recommendations are highlighted considering the current MP/MF research progress from COVID-related PPE waste.
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Affiliation(s)
- Muhammad Tariq Khan
- Department of Science and Environmental Studies, The Education University of Hong Kong, Tai po New Territories, Hong Kong
| | - Izaz Ali Shah
- State Key Joint Laboratory of Environmental Simulation and Pollution Control, School of Environment, Beijing Normal University, No. 19, Xinjiekouwai Street, Beijing 100875, China
| | - Md Faysal Hossain
- Department of Science and Environmental Studies, The Education University of Hong Kong, Tai po New Territories, Hong Kong; State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process, East China University of Science and Technology, No. 130, Meilong Road, Shanghai 200237, China
| | - Nasrin Akther
- State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process, East China University of Science and Technology, No. 130, Meilong Road, Shanghai 200237, China; Department of Soil Science, University of Chittagong, Chittagong 4331, Bangladesh
| | - Yanbo Zhou
- State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process, East China University of Science and Technology, No. 130, Meilong Road, Shanghai 200237, China
| | | | - Muayad Al-Shaeli
- Institute for Micro Process Engineering (IMVT), Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany
| | | | - Ihsanullah Ihsanullah
- Center for Environment and Water, Research Institute, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia.
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Fernandes S, Sosa-Napolskij M, Lobo G, Silva I. Relation of COVID-19 with liver diseases and their impact on healthcare systems: The Portuguese case. World J Gastroenterol 2023; 29:1109-1122. [PMID: 36844137 PMCID: PMC9950868 DOI: 10.3748/wjg.v29.i6.1109] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 11/18/2022] [Accepted: 12/30/2022] [Indexed: 02/10/2023] Open
Abstract
BACKGROUND The impact caused by the coronavirus disease 2019 (COVID-19) on the Portuguese population has been addressed in areas such as clinical manifestations, frequent comorbidities, and alterations in consumption habits. However, comorbidities like liver conditions and changes concerning the Portuguese population's access to healthcare-related services have received less attention. AIM To (1) Review the impact of COVID-19 on the healthcare system; (2) examine the relationship between liver diseases and COVID-19 in infected individuals; and (3) investigate the situation in the Portuguese population concerning these topics. METHODS For our purposes, we conducted a literature review using specific keywords. RESULTS COVID-19 is frequently associated with liver damage. However, liver injury in COVID-19 individuals is a multifactor-mediated effect. Therefore, it remains unclear whether changes in liver laboratory tests are associated with a worse prognosis in Portuguese individuals with COVID-19. CONCLUSION COVID-19 has impacted healthcare systems in Portugal and other countries; the combination of COVID-19 with liver injury is common. Previous liver damage may represent a risk factor that worsens the prognosis in individuals with COVID-19.
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Affiliation(s)
- Sara Fernandes
- Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto (ICBAS-UP), Porto 4050-313, Portugal
| | - Milaydis Sosa-Napolskij
- CINTESIS@RISE, Center for Health Technology and Services Research at The Associate Laboratory RISE–Health Research Network, Faculty of Medicine of The University of Porto, Porto 4200-219, Portugal
| | - Graça Lobo
- Laboratory of Pharmacology and Neurobiology–Department of Immuno-physiology and Pharmacology, Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto (ICBAS-UP), Porto 4050-313, Portugal
- Center for Drug Discovery and Innovative Medicines (MedInUP), Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto (ICBAS-UP), Porto 4050-313, Portugal
| | - Isabel Silva
- Laboratory of Pharmacology and Neurobiology–Department of Immuno-physiology and Pharmacology, Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto (ICBAS-UP), Porto 4050-313, Portugal
- Center for Drug Discovery and Innovative Medicines (MedInUP), Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto (ICBAS-UP), Porto 4050-313, Portugal
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Corrêa BSG, de Barros S, Vaz JB, Peres MA, Uchiyama MK, da Silva AA, Furukawa LNS. COVID-19: Understanding the impact of anti-hypertensive drugs and hydroxychloroquine on the ACE1 and ACE2 in lung and adipose tissue in SHR and WKY rats. Physiol Rep 2023; 11:e15598. [PMID: 36750199 PMCID: PMC9904959 DOI: 10.14814/phy2.15598] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 01/16/2023] [Accepted: 01/18/2023] [Indexed: 02/09/2023] Open
Abstract
Hypertensive individuals taking anti-hypertensive drugs from renin-angiotensin system inhibitors may exhibit a more severe evolution of the disease when contracting the SARS-CoV-2 virus (COVID-19 disease) due to potential increases in ACE2 expression. The study investigated ACE1 and ACE2 axes and hydroxychloroquine in the lungs and adipose tissue of male and female normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHRs). SHRs were treated with losartan (10 mg/kg/day) or captopril (10 mg/kg/day) for 14 days or 7 days with hydroxychloroquine (200 mg/kg/day) in drinking water. WKY rats were also treated for 7 days with hydroxychloroquine. Blood pressure (BP), protein, and mRNA expression of ACE1 and ACE2 were analyzed in serum, adipose, and lung tissues. Losartan and captopril reduced BP in both sexes in SHR, whereas hydroxychloroquine increased BP in WKY rats. Losartan reduced ACE2 in serum and lungs in both sexes and in adipose tissue of male SHRs. Captopril decreased ACE2 protein in the lung of females and in adipose tissue in both sexes of SHRs. Hydroxychloroquine decreased ACE1 and ACE2 proteins in the lungs in both sexes and adipose tissue in male SHRs. In female WKY rats, ACE2 protein was lower only in the lungs and adipose tissue. Losartan effectively inhibited ACE2 in male and captopril in female SHRs. Hydroxychloroquine inhibited ACE2 in male SHRs and female WKY rats. These results further our understanding of the ACE2 mechanism in patients under renin-angiotensin anti-hypertensive therapy and in many trials using hydroxychloroquine for COVID-19 treatment and potential sex differences in response to drug treatment.
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Affiliation(s)
- Beatriz Santos Geoffroy Corrêa
- Laboratory of Renal Pathophysiology, Department of Internal Medicine, School of MedicineUniversity of São PauloSão PauloBrazil
| | - Silvana de Barros
- Hypertension Unit, Renal Division, General Hospital of School of MedicineUniversity of São PauloSão PauloBrazil
| | - Julia Braga Vaz
- Laboratory of Renal Pathophysiology, Department of Internal Medicine, School of MedicineUniversity of São PauloSão PauloBrazil
| | - Maria Angelica Peres
- Laboratory of Renal Pathophysiology, Department of Internal Medicine, School of MedicineUniversity of São PauloSão PauloBrazil
| | - Mayara Klimuk Uchiyama
- Laboratory of Supramolecular Chemistry & Nanotechnology, Department of Fundamental Chemistry, Institute of ChemistryUniversity of São PauloSão PauloBrazil
| | - Alexandre Alves da Silva
- Department of Physiology and BiophysicsUniversity of Mississippi Medical Center JacksonJacksonMississippiUSA
| | - Luzia Naoko Shinohara Furukawa
- Laboratory of Renal Pathophysiology, Department of Internal Medicine, School of MedicineUniversity of São PauloSão PauloBrazil
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Panda SP, Reddy PH, Gorla US, Prasanth D. Neuroinflammation and neovascularization in diabetic eye diseases (DEDs): identification of potential pharmacotherapeutic targets. Mol Biol Rep 2023; 50:1857-1869. [PMID: 36513866 DOI: 10.1007/s11033-022-08113-6] [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: 09/23/2022] [Accepted: 11/09/2022] [Indexed: 12/15/2022]
Abstract
The goal of this review is to increase public knowledge of the etiopathogenesis of diabetic eye diseases (DEDs), such as diabetic retinopathy (DR) and ocular angiosarcoma (ASO), and the likelihood of blindness among elderly widows. A widow's life in North India, in general, is fraught with peril because of the economic and social isolation it brings, as well as the increased risk of death from heart disease, hypertension, diabetes, depression, and dementia. Neovascularization, neuroinflammation, and edema in the ocular tissue are hallmarks of the ASO, a rare form of malignant tumor. When diabetes, hypertension, and aging all contribute to increased oxidative stress, the DR can proceed to ASO. Microglia in the retina of the optic nerve head are responsible for causing inflammation, discomfort, and neurodegeneration. Those that come into contact with them will get blind as a result of this. Advanced glycation end products (AGE), vascular endothelial growth factor (VEGF), protein kinase C (PKC), poly-ADP-ribose polymerase (PARP), metalloproteinase9 (MMP9), nuclear factor kappaB (NFkB), program death ligand1 (PDL-1), factor VIII (FVIII), and von Willebrand factor (VWF) are potent agents for ocular neovascularisation (ONV), neuroinflammation and edema in the ocular tissue. AGE/VEGF, DAG/PKC, PARP/NFkB, RAS/VEGF, PDL-1/PD-1, VWF/FVIII/VEGF, and RAS/VEGF are all linked to the pathophysiology of DEDs. The interaction between ONV and ASO is mostly determined by the VWF/FVIII/VEGF and PDL-1/PD-1 axis. This study focused on retinoprotective medications that can pass the blood-retinal barrier and cure DEDs, as well as the factors that influence the etiology of neovascularization and neuroinflammation in the eye.
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Affiliation(s)
- Siva Prasad Panda
- Pharmacology Research Division, Institute of Pharmaceutical Research, GLA University, 281406, Mathura, Uttar Pradesh, India.
| | - P Hemachandra Reddy
- Department of Internal Medicine, Texas Tech University Health Sciences Center, 79430, Lubbock, TX, USA
- Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, 79430, Lubbock, TX, USA
- Department of Neurology, Texas Tech University Health Sciences Center, 79430, Lubbock, TX, USA
- Department of Public Health, Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, 79430, Lubbock, TX, USA
- Department of Speech, Language, and Hearing Sciences, Texas Tech University Health Sciences Center, 79430, Lubbock, TX, USA
| | - Uma Sankar Gorla
- College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Guntur, AP, India
| | - Dsnbk Prasanth
- Department of Pharmacognosy, KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada, AP, India
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Kumar A, Sharma A, Tirpude NV, Thakur S, Kumar S. Combating the Progression of Novel Coronavirus SARS-CoV-2 Infectious Disease: Current State and Future Prospects in Molecular Diagnostics and Drug Discovery. Curr Mol Med 2023; 23:127-146. [PMID: 34344288 DOI: 10.2174/1566524021666210803154250] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 04/07/2021] [Accepted: 04/14/2021] [Indexed: 12/16/2022]
Abstract
A highly infectious and life-threatening virus was first reported in Wuhan, China, in late 2019, and it rapidly spread all over the world. This novel virus belongs to the coronavirus family and is associated with severe acute respiratory syndrome (SARS), causing respiratory disease known as COVID-19. In March 2020, WHO has declared the COVID-19 outbreak a global pandemic. Its morbidity and mortality rates are swiftly rising day by day, with the situation becoming more severe and fatal for the comorbid population. Many COVID-19 patients are asymptomatic, but they silently spread the infection. There is a need for proper screening of infected patients to prevent the epidemic transmission of disease and for early curative interventions to reduce the risk of developing severe complications from COVID-19. To date, the diagnostic assays are of two categories, molecular detection of viral genetic material by real-time RTpolymerase chain reaction and serological test, which relies on detecting antiviral antibodies. Unfortunately, there are no effective prophylactics and therapeutics available against COVID-19. However, a few drugs have shown promising antiviral activity against it, and these presently are being referred for clinical trials, albeit FDA has issued an Emergency Use Authorization (EUA) for the emergency use of a few drugs for SARSCoV- 2 infection. This review provides an insight into current progress, challenges and future prospects of laboratory detection methods of COVID-19, and highlights the clinical stage of the major evidence-based drugs/vaccines recommended against the novel SARS-CoV-2 pandemic virus.
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Affiliation(s)
- Arbind Kumar
- COVID-19 Testing Facility, CSIR-Institute of Himalayan Bioresource& Technology (IHBT), Palampur, India
| | - Aashish Sharma
- COVID-19 Testing Facility, CSIR-Institute of Himalayan Bioresource& Technology (IHBT), Palampur, India
| | - Narendra Vijay Tirpude
- COVID-19 Testing Facility, CSIR-Institute of Himalayan Bioresource& Technology (IHBT), Palampur, India
| | - Sharad Thakur
- COVID-19 Testing Facility, CSIR-Institute of Himalayan Bioresource& Technology (IHBT), Palampur, India
| | - Sanjay Kumar
- COVID-19 Testing Facility, CSIR-Institute of Himalayan Bioresource& Technology (IHBT), Palampur, India
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24
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Said ASA, Hussein RRS, Khalil DM, Fahmy AM, Hassanein AHA, Abdelaty LN. Monotherapy versus polytherapy of enoxaparin and hydroxychloroquine for the treatment of COVID-19: A randomized controlled clinical trial. Pharm Pract (Granada) 2023; 21:2777. [PMID: 37090452 PMCID: PMC10117317 DOI: 10.18549/pharmpract.2023.1.2777] [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: 09/26/2022] [Accepted: 11/03/2022] [Indexed: 04/08/2023] Open
Abstract
Objectives The current study aims to assess the efficacy and safety of Enoxaparin and hydroxychloroquine (HCQ) used as monothrapy or polytherapy versus standard care alone in Coronavirus 2019 (COVID-19) infected patients. Methods The current study included two hundred patients with laboratory confirmed COVID-19 infection. Patients admitted to hospital were randomly allocated into four groups: group I: received standard COVID-19 therapy, group II: received Enoxaparin 40mg/day subcutaneously (SC) plus standard therapy, group III: received 400 mg/day HCQ plus standard therapy & group IV: received a combination of 400 mg/day HCQ and Enoxaparin plus standard COVID-19 therapy. The disease progression was evaluated by duration to a negative polymerase chain reaction (PCR), length of hospital or Intensive Care Unit (ICU) stay, and mortality rate. The safety of treatments was evaluated by measuring adverse effects. Results The length of hospital stay, ICU admission and mortality were significantly decreased in Enoxaparin plus standard COVID-19 therapy group versus other groups. Conclusion These findings suggest that Enoxaparin was safe, effective, and well tolerated and has a role in decreasing the progression of the disease and its complications while HCQ did not discover any evidence of extra therapeutic benefits.
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Affiliation(s)
- Amira S A Said
- PhD. Department of Clinical Pharmacy, College of Pharmacy, Al Ain University, Al Ain, Abu Dhabi, UAE. Department of Clinical Pharmacy, Faculty of Pharmacy, Beni-Suef University, Egypt.
| | - Raghda R S Hussein
- PhD. Department of Clinical Pharmacy, Faculty of Pharmacy, Beni-Suef University, Egypt. Department of Clinical Pharmacy, Faculty of Pharmacy, October 6 University, Egypt.
| | - Doaa Mahmoud Khalil
- MD. Department of Public Health & Community Medicine, Faculty of Medicine, Beni-Suef University, Egypt.
| | - Alzhraa M Fahmy
- MD. Department of Tropical Medicine & Infectious Diseases, Faculty of Medicine, Beni-Suef University, Egypt.
| | - Ahmed H A Hassanein
- PhD. Phd of Biotechnology, Faculty of Postgraduate Studies for Advanced Science, Beni-Suef University, Egypt.
| | - Lamiaa N Abdelaty
- PhD. Department of Clinical Pharmacy, Faculty of Pharmacy, October 6 University, Egypt.
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25
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Prasanth DSNBK, Murahari M, Chandramohan V, Guntupalli C, Atmakuri LR. Computational study for identifying promising therapeutic agents of hydroxychloroquine analogues against SARS-CoV-2. J Biomol Struct Dyn 2022; 40:11822-11836. [PMID: 34396938 DOI: 10.1080/07391102.2021.1965027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Hydroxychloroquine (HCQ) and its derivatives have recently gained tremendous attention as a probable medicinal agent in the COVID-19 outbreak caused by SARS-CoV-2. An efficient agent to act directly in inhibiting the SARS-CoV-2 replication is yet to be achieved. Thus, the goal is to investigate the dynamic nature of HCQ derivatives against SARS-CoV-2 main protease and spike proteins. Molecular docking studies were also performed to understand their binding affinity in silico methods using the vital protein domains and enzymes involved in replicating and multiplying SARS-CoV-2, which were the main protease and spike protein. Molecular Dynamic simulations integrated with MM-PBSA calculations have identified In silico potential inhibitors ZINC05135012 and ZINC59378113 against the main protease with -185.171 ± 16.388, -130.759 ± 15.741 kJ/mol respectively, ZINC16638693 and ZINC59378113 against spike protein -141.425 ± 22.447, -129.149 ± 11.449 kJ/mol. Identified Hit molecules had demonstrated Drug Likeliness features, PASS values and ADMET predictions with no violations. Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- D S N B K Prasanth
- Pharmacognosy Research Division, K L College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, India
| | - Manikanta Murahari
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, Bangalore, India
| | - Vivek Chandramohan
- Department of Biotechnology, Siddaganga Institute of Technology, Tumakuru, India
| | - Chakravarthi Guntupalli
- Pharmacognosy Research Division, K L College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, India
| | - Lakshmana Rao Atmakuri
- Department of Pharmaceutical Analysis, V. V. Institute of Pharmaceutical Sciences, Gudlavalleru, India
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26
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Trivedi A, Ahmad R, Siddiqui S, Misra A, Khan MA, Srivastava A, Ahamad T, Khan MF, Siddiqi Z, Afrin G, Gupta A, Upadhyay S, Husain I, Ahmad B, Mehrotra S, Kant S. Prophylactic and therapeutic potential of selected immunomodulatory agents from Ayurveda against coronaviruses amidst the current formidable scenario: an in silico analysis. J Biomol Struct Dyn 2022; 40:9648-9700. [PMID: 34243689 DOI: 10.1080/07391102.2021.1932601] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
There is currently a dearth of specific therapies to treat respiratory infections caused by the three related species of coronaviruses viz. SARS-CoV-2, SARS-CoV and MERS-CoV. Prevention from disease is currently the safest and most convenient alternative available. The present study aimed to evaluate the preventive and therapeutic effect of fifteen phytoconstituents from medicinal plants of Ayurveda against coronaviruses by in silico screening. All the phytoconstituents exhibited rapid GI absorption and bioavailability and most of them had no toxicity versus reference drug chloroquine. BAS analyses revealed that most of the phytocomponents had favorable bioactivity scores towards biological target proteins. Principal component analysis revealed that most of the phytoconstituents fell close to chloroquine in 3D projection of chemical space. Affinity of phytoconstituents towards SARS-CoV-2 spike protein-human ACE2 complex decreased as isomeldenin > tinosporaside > EGCG whereas in case of unbound ACE2, the strength of binding followed the order isomeldenin > tinosporaside > ellagic acid. Towards SARS-CoV-2 main and papain-like proteases, the affinity decreased as isomeldenin > EGCG > tinosporaside and EGCG > tinosporaside > isomeldenin, respectively. Most phytoconstituents displayed significant binding kinetics to the selected protein targets than chloroquine. SAR analysis revealed that isomeldenin, tinosporaside, EGCG and ellagic acid bind to viral spike glycoproteins via H-bond, Pi-Pi, Pi-sigma and Pi-alkyl type interactions. Molecular dynamics simulation of isomeldenin and EGCG with SARS-CoV and SARS-CoV-2 spike glycoproteins exhibited low deviations throughout the 100 ns simulation indicating good stability and compactness of the protein-ligand complexes. Thus, the above four phytoconstituents have the potential to emerge as prophylactic and therapeutic agents against coronaviruses if investigated further in vitro and in vivo.
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Affiliation(s)
- Anchal Trivedi
- Department of Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | - Rumana Ahmad
- Department of Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | - Sahabjada Siddiqui
- Department of Biotechnology, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | - Aparna Misra
- Department of Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | | | - Aditi Srivastava
- Department of Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | - Tanveer Ahamad
- Department of Biotechnology, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | - Mohd Faheem Khan
- Department of Biotechnology, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | - Zeba Siddiqi
- Department of Medicine, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | - Gazala Afrin
- Department of Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | - Anamika Gupta
- Department of Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | - Shivbrat Upadhyay
- Department of Biotechnology, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | - Ishrat Husain
- Department of Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | - Bilal Ahmad
- Research Cell, Era's Lucknow Medical College and Hospital, Era University, Lucknow, Uttar Pradesh, India
| | - Sudhir Mehrotra
- Department of Biochemistry, University of Lucknow, Lucknow, Uttar Pradesh, India
| | - Surya Kant
- Department of Respiratory Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
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27
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Shahrin L, Mahfuz M, Rahman MW, Hossain MR, Khandaker AM, Alam MA, Osmany DMMF, Islam MM, Chisti MJ, Ahmed CM, Ahmed T. Hospital-Based Quasi-Experimental Study on Hydroxychloroquine Pre-Exposure Prophylaxis for COVID-19 in Healthcare Providers with Its Potential Side-Effects. Life (Basel) 2022; 12:2047. [PMID: 36556412 PMCID: PMC9786013 DOI: 10.3390/life12122047] [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: 10/22/2022] [Revised: 11/24/2022] [Accepted: 11/30/2022] [Indexed: 12/12/2022] Open
Abstract
Considering that it has been more than 24 months since SARS-CoV-2 emerged, it is crucial to identify measures that prevent and control pathogen transmission in workplace settings. Our aim was to report results of a hospital-based program that delivered hydroxychloroquine (HCQ) tablets as COVID-19 prophylaxis to the frontline healthcare workers (HCW)s who cared for COVID-19 patients and to evaluate the efficacy of HCQ. Setting and participants: Quasi-experimental, controlled, single-center study. The included participants were doctors, nurses, health workers, cleaning staff, and non-healthcare supportive staff. The main outcome was contracting COVID-19 anytime during the period of taking the prophylaxis, confirmed by RT-PCR. A total of 336 participants, without any clinical evidence of COVID-19 and without any known contact with family members, were included in the trial; 230 were assigned to HCQ and 106 declined to take any drug. Results: Among the participants, 43 (18.7%) in the HCQ group and 11 (10.4%) participants in the control group developed COVID-19. For the evaluation of side effects, we evaluated 12-lead ECGs of both groups at the baseline and after 4 weeks to monitor QTc interval. A total of 91% (198 of 217) participants in the prophylaxis group and 92% (11 of 12) in the control group had a QTc < 45o msec, which is within normal limits. Conclusions: Although the number of symptomatic infections in health personnel was lower in the control group, the difference was not statistically significant. However, in the absence of any effective pre-exposure prophylaxis medicine for COVID-19, practicing proper infection prevention and control (IPC) and vaccination is the only way forward.
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Affiliation(s)
- Lubaba Shahrin
- Dhaka Hospital, International Centre for Diarrheal Disease Research, Bangladesh (icddr, b), Dhaka 1212, Bangladesh
- Nutrition and Clinical Services Division, International Centre for Diarrheal Disease Research, Bangladesh (icddr, b), Dhaka 1212, Bangladesh
| | - Mustafa Mahfuz
- Nutrition and Clinical Services Division, International Centre for Diarrheal Disease Research, Bangladesh (icddr, b), Dhaka 1212, Bangladesh
| | - Md. Waliur Rahman
- Nutrition and Clinical Services Division, International Centre for Diarrheal Disease Research, Bangladesh (icddr, b), Dhaka 1212, Bangladesh
| | - Md. Rezaul Hossain
- Department of Epidemiology, University of Washington, Seattle, WA 98195, USA
| | | | - Md. Ashraful Alam
- Nutrition and Clinical Services Division, International Centre for Diarrheal Disease Research, Bangladesh (icddr, b), Dhaka 1212, Bangladesh
| | - Din M. M. F. Osmany
- Department of Cardiology, Bangabandhu Sheikh Mujib Medical University, Dhaka 1000, Bangladesh
| | - Md. Munirul Islam
- Nutrition and Clinical Services Division, International Centre for Diarrheal Disease Research, Bangladesh (icddr, b), Dhaka 1212, Bangladesh
| | - Mohammod Jobayer Chisti
- Dhaka Hospital, International Centre for Diarrheal Disease Research, Bangladesh (icddr, b), Dhaka 1212, Bangladesh
- Nutrition and Clinical Services Division, International Centre for Diarrheal Disease Research, Bangladesh (icddr, b), Dhaka 1212, Bangladesh
| | - Chaudhury Meshkat Ahmed
- Department of Cardiology, Bangabandhu Sheikh Mujib Medical University, Dhaka 1000, Bangladesh
| | - Tahmeed Ahmed
- Nutrition and Clinical Services Division, International Centre for Diarrheal Disease Research, Bangladesh (icddr, b), Dhaka 1212, Bangladesh
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28
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Li X, Wang W, Yan S, Zhao W, Xiong H, Bao C, Chen J, Yue Y, Su Y, Zhang C. Drug-induced liver injury in COVID-19 treatment: Incidence, mechanisms and clinical management. Front Pharmacol 2022; 13:1019487. [PMID: 36518661 PMCID: PMC9742434 DOI: 10.3389/fphar.2022.1019487] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 11/14/2022] [Indexed: 07/21/2023] Open
Abstract
The COVID-19 outbreak triggered a serious and potentially lethal pandemic, resulting in massive health and economic losses worldwide. The most common clinical manifestations of COVID-19 patients are pneumonia and acute respiratory distress syndrome, with a variety of complications. Multiple organ failure and damage, ultimately leading to patient death, are possible as a result of medication combinations, and this is exemplified by DILI. We hope to summarize DILI caused by the antiviral drugs favipiravir, remdesivir, lopinavir/ritonavir, and hydroxychloroquine in COVID-19 patients in this review. The incidence of liver injury in the treatment of COVID-19 patients was searched on PubMed to investigate DILI cases. The cumulative prevalence of acute liver injury was 23.7% (16.1%-33.1%). We discuss the frequency of these events, potential mechanisms, and new insights into surveillance strategies. Furthermore, we also describe medication recommendations aimed at preserving DILI caused by treatment in COVID-19 patients.
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Affiliation(s)
- Xichuan Li
- Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, Tianjin, China
| | - Wanting Wang
- Department of Colorectal Surgery, Tianjin Institute of Coloproctology, The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, China
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Suying Yan
- Department of Colorectal Surgery, Tianjin Institute of Coloproctology, The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, China
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Weipeng Zhao
- Department of Breast Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China
| | - Hui Xiong
- School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China
| | - Cuiping Bao
- Departments of Radiology, Tianjin Union Medical Center, Tianjin, China
| | - Jinqian Chen
- Departments of Pharmacy, NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital, Tianjin, China
| | - Yuan Yue
- Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, Tianjin, China
| | - Yanjun Su
- Department of Lung Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China
| | - Chunze Zhang
- Department of Colorectal Surgery, Tianjin Institute of Coloproctology, The Institute of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, China
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29
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COVID-19 Infection in Rheumatic Patients on Chronic Antimalarial Drugs: A Systematic Review and Meta-Analysis. J Clin Med 2022; 11:jcm11226865. [PMID: 36431342 PMCID: PMC9693294 DOI: 10.3390/jcm11226865] [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: 10/24/2022] [Revised: 11/18/2022] [Accepted: 11/18/2022] [Indexed: 11/23/2022] Open
Abstract
The ongoing chronic use of hydroxychloroquine or chloroquine (HCQ/CQ) in rheumatic patients might impact their outcomes after a SARS-CoV-2 infection. Therefore, we sought to assess the mortality in rheumatic patients with chronic HCQ/CQ use who developed a COVID-19 infection through a comparison between individuals chronically using HCQ/CQ with those not taking these drugs. We performed a systematic review and meta-analysis of studies on PubMed, Embase, and Cochrane Central. We included full-length reports, prospective observational cohorts, and clinical trials of adult patients (aged ≥ 18 years) who were diagnosed with a COVID-19 infection. Case studies, case series, letters, comments, and editorials were excluded. The main outcome was all-cause mortality. This study is registered with PROSPERO (CRD42022341678). We identified 541 studies, of which 20 studies were included, comprising 236,997 patients. All-cause mortality was significantly lower in patients with prior chronic use of HCQ/CQ compared to those with no previous usage (OR 0.76; 95% CI 0.62-0.94; p = 0.01). There was a considerably lower incidence of hospitalization among patients with chronic HCQ/CQ use compared to their counterparts without HCQ/CQ usage (OR 0.80; 95% CI 0.65-0.99; p = 0.04). All-cause mortality and hospitalization were significantly lower in rheumatic patients with chronic HCQ/CQ use who developed a COVID-19 infection.
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30
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Ruiz HK, Serrano DR, Calvo L, Cabañas A. Current Treatments for COVID-19: Application of Supercritical Fluids in the Manufacturing of Oral and Pulmonary Formulations. Pharmaceutics 2022; 14:2380. [PMID: 36365198 PMCID: PMC9697571 DOI: 10.3390/pharmaceutics14112380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 10/23/2022] [Accepted: 10/28/2022] [Indexed: 10/06/2024] Open
Abstract
Even though more than two years have passed since the emergence of COVID-19, the research for novel or repositioned medicines from a natural source or chemically synthesized is still an unmet clinical need. In this review, the application of supercritical fluids to the development of novel or repurposed medicines for COVID-19 and their secondary bacterial complications will be discussed. We envision three main applications of the supercritical fluids in this field: (i) drug micronization, (ii) supercritical fluid extraction of bioactives and (iii) sterilization. The supercritical fluids micronization techniques can help to improve the aqueous solubility and oral bioavailability of drugs, and consequently, the need for lower doses to elicit the same pharmacological effects can result in the reduction in the dose administered and adverse effects. In addition, micronization between 1 and 5 µm can aid in the manufacturing of pulmonary formulations to target the drug directly to the lung. Supercritical fluids also have enormous potential in the extraction of natural bioactive compounds, which have shown remarkable efficacy against COVID-19. Finally, the successful application of supercritical fluids in the inactivation of viruses opens up an opportunity for their application in drug sterilization and in the healthcare field.
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Affiliation(s)
- Helga K. Ruiz
- Department of Physical Chemistry, Complutense University of Madrid, 28040 Madrid, Spain
| | - Dolores R. Serrano
- Department of Pharmaceutics and Food Technology, Complutense University of Madrid, 28040 Madrid, Spain
| | - Lourdes Calvo
- Department of Chemical Engineering, Complutense University of Madrid, 28040 Madrid, Spain
| | - Albertina Cabañas
- Department of Physical Chemistry, Complutense University of Madrid, 28040 Madrid, Spain
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31
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Delen LA, Gok A, Kasapoglu US, Cagasar O, Gok Z, Berber N, Derya S, Tetik B. EFFECTS OF HYDROXYCHLOROQUINE PLUS FAVIPIRAVIR TREATMENT ON THE CLINICAL COURSE AND BIOMARKERS IN HOSPITALIZED COVID-19 PATIENTS WITH PNEUMONIA. Acta Clin Croat 2022; 61:403-411. [PMID: 37492367 PMCID: PMC10364115 DOI: 10.20471/acc.2022.61.03.05] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Accepted: 06/25/2021] [Indexed: 07/27/2023] Open
Abstract
Background The novel coronavirus disease 2019 (COVID-19) has a broad spectrum of clinical manifestations, the most common serious clinical manifestation of the coronavirus infection being pneumonia. Unfortunately, the optimal treatment approach is still uncertain. However, many studies have been conducted on the effectiveness of several medications in the treatment of COVID-19 infection. The aim of this study was to evaluate the effectiveness of the hydroxychloroquine (HCQ) + favipiravir (FAV) treatment regimen and HCQ alone by comparing the patient's clinical response and laboratory results on the fifth day of treatment in patients hospitalized due to COVID-19 infection. Patients and methods This retrospective cohort study was conducted in Malatya Training and Research Hospital between March 2020 and July 2020. The study included 69 patients with confirmed COVID-19 with pneumonia. The patients were divided into 2 groups, those receiving HCQ alone and those receiving the HCQ + FAV combination. Results A total of 69 patients were included in the study, and the mean age was 60.09±15.56 years. A statistically significant decrease was observed in C-reactive protein (CRP) levels, at the end of the fifth day, in patients who received HCQ + FAV treatment (p=0.002), whereas there was no decrease in CRP levels in patients who received HCQ treatment alone. In addition, an increase in lymphocyte count and a better fever response was observed at the end of the fifth day in patients who received HCQ + FAV (p=0.008). However, there was no statistical difference between both treatment regimens in terms of hospital stay and treatment results (p=0.008, p=0.744, p=0.517). Conclusion Although the combination of HCQ + FAV treatment was observed to be effective on CRP levels and fever response in patients with COVID-19 pneumonia, there was no difference in terms of hospital stay and discharge.
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Affiliation(s)
- Leman Acun Delen
- Department of Anesthesiology and Reanimation, Turgut Ozal University, Malatya Training and Research Hospital, Malatya, Turkey
| | - Abdullah Gok
- Department of Anesthesiology and Reanimation, Turgut Ozal University, Malatya Training and Research Hospital, Malatya, Turkey
| | - Umut Sabri Kasapoglu
- Department of Critical Care Medicine, Turgut Ozal University, Malatya Training and Research Hospital, Malatya, Turkey
| | - Ozlem Cagasar
- Department of Infectious Diseases and Clinical Microbiology, Turgut Ozal University, Malatya Training and Research Hospital, Malatya, Turkey
| | - Zarife Gok
- Department of Ophthalmology, Turgut Ozal University, Malatya Training and Research Hospital, Malatya, Turkey
| | - Nurcan Berber
- Department of Chest Diseases, Turgut Ozal University, Malatya Training and Research Hospital, Malatya, Turkey
| | - Serdar Derya
- Department of Traumatology and Emergency Medicine, Turgut Ozal University, Malatya Training and Research Hospital, Malatya, Turkey
| | - Bora Tetik
- Department of Neurosurgery, Inonu University School of Medicine, Malatya, Turkey
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Axelerad A, Stuparu AZ, Muja LF, Docu Axelerad S, Petrov SG, Gogu AE, Jianu DC. Narrative Review of New Insight into the Influence of the COVID-19 Pandemic on Cardiovascular Care. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:1554. [PMID: 36363511 PMCID: PMC9694465 DOI: 10.3390/medicina58111554] [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: 09/25/2022] [Revised: 10/21/2022] [Accepted: 10/26/2022] [Indexed: 09/10/2024]
Abstract
Background and Objectives: The purpose of this paper was to perform a literature review on the effects of the COVID-19 pandemic on cardiothoracic and vascular surgery care and departments. Materials and Methods: To conduct this evaluation, an electronic search of many databases was conducted, and the resulting papers were chosen and evaluated. Results: Firstly, we have addressed the impact of COVID-19 infection on the cardiovascular system from the pathophysiological and treatment points of view. Afterwards, we analyzed every cardiovascular disease that seemed to appear after a COVID-19 infection, emphasizing the treatment. In addition, we have analyzed the impact of the pandemic on the cardiothoracic and vascular departments in different countries and the transitions that appeared. Finally, we discussed the implications of the cardiothoracic and vascular specialists' and residents' work and studies on the pandemic. Conclusions: The global pandemic caused by SARS-CoV-2 compelled the vascular profession to review the treatment of certain vascular illnesses and find solutions to address the vascular consequences of COVID-19 infection. The collaboration between vascular surgeons, public health specialists, and epidemiologists must continue to investigate the impact of the pandemic and the response to the public health issue.
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Affiliation(s)
- Any Axelerad
- Department of Neurology, General Medicine Faculty, ‘Ovidius’ University, 900470 Constanta, Romania
- Department of Neurology, ‘Sf. Ap. Andrei’ County Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | - Alina Zorina Stuparu
- Department of Neurology, General Medicine Faculty, ‘Ovidius’ University, 900470 Constanta, Romania
- Department of Neurology, ‘Sf. Ap. Andrei’ County Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | - Lavinia Florenta Muja
- Department of Neurology, General Medicine Faculty, ‘Ovidius’ University, 900470 Constanta, Romania
- Department of Neurology, ‘Sf. Ap. Andrei’ County Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | | | - Silvia Georgeta Petrov
- Doctoral School of the Faculty of Psychology and Educational Sciences within the University of Bucharest, 050663 Bucharest, Romania
| | - Anca Elena Gogu
- Department of Neurology, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania
- Centre for Cognitive Research in Neuropsychiatric Pathology (Neuropsy-Cog), Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania
| | - Dragos Catalin Jianu
- Department of Neurology, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania
- Centre for Cognitive Research in Neuropsychiatric Pathology (Neuropsy-Cog), Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania
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Targeted therapy in Coronavirus disease 2019 (COVID-19): Implication from cell and gene therapy to immunotherapy and vaccine. Int Immunopharmacol 2022; 111:109161. [PMID: 35998506 PMCID: PMC9385778 DOI: 10.1016/j.intimp.2022.109161] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 07/27/2022] [Accepted: 08/11/2022] [Indexed: 02/07/2023]
Abstract
Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is a highly pathogenic and transmissible virus. Infection caused by SARS-CoV-2 known as Coronavirus disease 2019 (COVID-19) can be severe, especially among high risk populations affected of underlying medical conditions. COVID-19 is characterized by the severe acute respiratory syndrome, a hyper inflammatory syndrome, vascular injury, microangiopathy and thrombosis. Antiviral drugs and immune modulating methods has been evaluated. So far, a particular therapeutic option has not been approved for COVID-19 and a variety of treatments have been studied for COVID-19 including, current treatment such as oxygen therapy, corticosteroids, antiviral agents until targeted therapy and vaccines which are diverse in each patient and have various outcomes. According to the findings of different in vitro and in vivo studies, some novel approach such as gene editing, cell based therapy, and immunotherapy may have significant potential in the treatment of COVID-19. Based on these findings, this paper aims to review the different strategies of treatment against COVID-19 and provide a summary from traditional and newer methods in curing COVID-19.
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Singh M, Jayant K, Singh D, Bhutani S, Poddar NK, Chaudhary AA, Khan SUD, Adnan M, Siddiqui AJ, Hassan MI, Khan FI, Lai D, Khan S. Withania somnifera (L.) Dunal (Ashwagandha) for the possible therapeutics and clinical management of SARS-CoV-2 infection: Plant-based drug discovery and targeted therapy. Front Cell Infect Microbiol 2022; 12:933824. [PMID: 36046742 PMCID: PMC9421373 DOI: 10.3389/fcimb.2022.933824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Accepted: 07/11/2022] [Indexed: 11/23/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) pandemic has killed huge populations throughout the world and acts as a high-risk factor for elderly and young immune-suppressed patients. There is a critical need to build up secure, reliable, and efficient drugs against to the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Bioactive compounds of Ashwagandha [Withania somnifera (L.) Dunal] may implicate as herbal medicine for the management and treatment of patients infected by SARS-CoV-2 infection. The aim of the current work is to update the knowledge of SARS-CoV-2 infection and information about the implication of various compounds of medicinal plant Withania somnifera with minimum side effects on the patients' organs. The herbal medicine Withania somnifera has an excellent antiviral activity that could be implicated in the management and treatment of flu and flu-like diseases connected with SARS-CoV-2. The analysis was performed by systematically re-evaluating the published articles related to the infection of SARS-CoV-2 and the herbal medicine Withania somnifera. In the current review, we have provided the important information and data of various bioactive compounds of Withania somnifera such as Withanoside V, Withanone, Somniferine, and some other compounds, which can possibly help in the management and treatment of SARS-CoV-2 infection. Withania somnifera has proved its potential for maintaining immune homeostasis of the body, inflammation regulation, pro-inflammatory cytokines suppression, protection of multiple organs, anti-viral, anti-stress, and anti-hypertensive properties. Withanoside V has the potential to inhibit the main proteases (Mpro) of SARS-CoV-2. At present, synthetic adjuvant vaccines are used against COVID-19. Available information showed the antiviral activity in Withanoside V of Withania somnifera, which may explore as herbal medicine against to SARS-CoV-2 infection after standardization of parameters of drug development and formulation in near future.
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Affiliation(s)
- Manali Singh
- Department of Biotechnology, Invertis University, Bareilly, Uttar Pradesh, India
- Department of Biochemistry, C.B.S.H, G.B Pant University of Agriculture and Technology, Pantnagar, Uttrakhand, India
| | - Kuldeep Jayant
- Department of Agricultural and Food Engineering, IIT Kharagpur, West Bengal, Kharagpur, India
| | - Dipti Singh
- Department of Biochemistry, C.B.S.H, G.B Pant University of Agriculture and Technology, Pantnagar, Uttrakhand, India
| | - Shivani Bhutani
- Department of Biotechnology, Invertis University, Bareilly, Uttar Pradesh, India
| | - Nitesh Kumar Poddar
- Department of Biosciences, Manipal University Jaipur, Jaipur, Rajasthan, India
| | - Anis Ahmad Chaudhary
- Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia
| | - Salah-Ud-Din Khan
- Department of Biochemistry, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia
| | - Mohd Adnan
- Department of Biology, College of Science, University of Hail, Hail, Saudi Arabia
| | - Arif Jamal Siddiqui
- Department of Biology, College of Science, University of Hail, Hail, Saudi Arabia
| | - Md Imtaiyaz Hassan
- Center for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India
| | - Faez Iqbal Khan
- Department of Biological Sciences, School of Science, Xi’an Jiaotong-Liverpool University, Suzhou, China
- School of Electronic Science and Engineering, University of Electronic Science and Technology of China, Chengdu, China
| | - Dakun Lai
- School of Electronic Science and Engineering, University of Electronic Science and Technology of China, Chengdu, China
| | - Shahanavaj Khan
- Department of Health Sciences, Novel Global Community Educational Foundation 7 Peterlee Place, Hebersham, NSW, Australia
- Department of Medical Lab Technology, Indian Institute of Health and Technology (IIHT), Deoband, Saharanpur, UP, India
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
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Angiotensin II Exaggerates SARS-CoV-2 Specific T-Cell Response in Convalescent Individuals following COVID-19. Int J Mol Sci 2022; 23:ijms23158669. [PMID: 35955801 PMCID: PMC9368904 DOI: 10.3390/ijms23158669] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Revised: 07/28/2022] [Accepted: 08/02/2022] [Indexed: 12/10/2022] Open
Abstract
Dysregulation of renin−angiotensin systems during coronavirus disease 2019 (COVID-19) infection worsens the symptoms and contributes to COVID-19 severity and mortality. This study sought to investigate the effect of exogenous angiotensin II (Ang-II) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T-cells response in recovered COVID-19 patients. Human peripheral blood mononuclear cells (PBMCs) were treated with Ang II and then stimulated with a SARS-CoV-2 peptide pool. T-cell responses were measured using flow cytometry, while enzyme-linked immunosorbent assay (ELISA) and intracellular cytokine staining (ICS) assays determined functional capability and polarization. Additionally, the relative level of protein phosphorylation was measured using a phosphokinase array. Our results showed that Ang II treatment significantly increased the magnitude of SARS-CoV-2-specific T-cell response in stimulated PBMCs with a SARS-CoV-2 peptide pool. Moreover, the phosphorylation levels of numerous proteins implicated in cardiovascular diseases, inflammation, and viral infection showed significant increases in the presence of Ang II. The mitogenic stimulation of PBMCs after Ang II and SARS-CoV-2 peptide pool stimulation showed functional polarization of T-cells toward Th1/Th17 and Th17 phenotypes, respectively. Meanwhile, ELISA showed increased productions of IL-1β and IL-6 in Ang II-stimulated PBMCs without affecting the IL-10 level. To our knowledge, this study is the first to demonstrate that Ang II exaggerates SARS-CoV-2-specific T-cells response. Therefore, during COVID-19 infection, Ang II may aggravate the inflammatory response and change the immune response toward a more inflammatory profile against SARS-CoV-2 infection.
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36
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CD4+ Cytotoxic T Cells Involved in the Development of EBV-Associated Diseases. Pathogens 2022; 11:pathogens11080831. [PMID: 35894054 PMCID: PMC9330826 DOI: 10.3390/pathogens11080831] [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: 06/27/2022] [Revised: 07/17/2022] [Accepted: 07/22/2022] [Indexed: 11/17/2022] Open
Abstract
Activated cytotoxic CD4 T cells (HLA-DR+) play an important role in the control of EBV infection, especially in cells with latency I (EBNA-1). One of the evasion mechanisms of these latency cells is generated by gp42, which, via peripherally binding to the β1 domain of the β chain of MHC class II (HLA-DQ, -DR, and -DP) of the infected B lymphocyte, can block/alter the HLA class II/T-cell receptor (TCR) interaction, and confer an increased level of susceptibility towards the development of EBV-associated autoimmune diseases or cancer in genetically predisposed individuals (HLA-DRB1* and DQB1* alleles). The main developments predisposing the factors of these diseases are: EBV infection; HLA class II risk alleles; sex; and tissue that is infiltrated with EBV-latent cells, forming ectopic lymphoid structures. Therefore, there is a need to identify treatments for eliminating cells with EBV latency, because the current treatments (e.g., antivirals and rituximab) are ineffective.
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Khabyah AA, Jamil MK, Koam ANA, Javed A, Azeem M. Partition dimension of COVID antiviral drug structures. MATHEMATICAL BIOSCIENCES AND ENGINEERING : MBE 2022; 19:10078-10095. [PMID: 36031984 DOI: 10.3934/mbe.2022471] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
In November 2019, there was the first case of COVID-19 (Coronavirus) recorded, and up to 3$ ^{rd }$ of April 2020, 1,116,643 confirmed positive cases, and around 59,158 dying were recorded. Novel antiviral structures of the SARS-COV-2 virus is discussed in terms of the metric basis of their molecular graph. These structures are named arbidol, chloroquine, hydroxy-chloroquine, thalidomide, and theaflavin. Partition dimension or partition metric basis is a concept in which the whole vertex set of a structure is uniquely identified by developing proper subsets of the entire vertex set and named as partition resolving set. By this concept of vertex-metric resolvability of COVID-19 antiviral drug structures are uniquely identified and helps to study the structural properties of structure.
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Affiliation(s)
- Ali Al Khabyah
- Department of Mathematics, College of Science, Jazan University, New Campus, Jazan 2097, Saudi Arabia
| | - Muhammad Kamran Jamil
- Department of Mathematics, Riphah Institute of Computing and Applied Sciences, Riphah International University Lahore, Pakistan
| | - Ali N A Koam
- Department of Mathematics, College of Science, Jazan University, New Campus, Jazan 2097, Saudi Arabia
| | - Aisha Javed
- Abdus Salam School of Mathematical Sciences, Government College University, Lahore, Pakistan
| | - Muhammad Azeem
- Department of Mathematics, Riphah Institute of Computing and Applied Sciences, Riphah International University Lahore, Pakistan
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38
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Boadu A, Agoni C, Karpoormath R, Soliman M, Nlooto M. Repurposing antiviral phytochemicals from the leaf extracts of Spondias mombin (Linn) towards the identification of potential SARSCOV-2 inhibitors. Sci Rep 2022; 12:10896. [PMID: 35764663 PMCID: PMC9240089 DOI: 10.1038/s41598-022-14558-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 06/08/2022] [Indexed: 11/30/2022] Open
Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a pneumonia-like disease with a pattern of acute respiratory symptoms, currently remains a significant public health concern causing tremendous human suffering. Although several approved vaccines exist, vaccine hesitancy, limited vaccine availability, high rate of viral mutation, and the absence of approved drugs account for the persistence of SARS-CoV-2 infections. The investigation of possibly repurposing of phytochemical compounds as therapeutic alternatives has gained momentum due to their reported affordability and minimal toxicity. This study investigated anti-viral phytochemical compounds from ethanolic leaf extracts of Spondias mombin L as potential inhibitor candidates against SARS-CoV-2. We identified Geraniin and 2-O-Caffeoyl-(+)-allohydroxycitric acid as potential SARS-CoV-2 inhibitor candidates targeting the SARS-CoV-2 RNA-dependent polymerase receptor-binding domain (RBD) of SARS-CoV-2 viral S-protein and the 3C-like main protease (3CLpro). Geraniin exhibited binding free energy (ΔGbind) of - 25.87 kcal/mol and - 21.74 kcal/mol towards SARS-CoV-2 RNA-dependent polymerase and receptor-binding domain (RBD) of SARS-CoV-2 viral S-protein respectively, whereas 2-O-Caffeoyl-(+)-allohydroxycitric acid exhibited a ΔGbind of - 32 kcal/mol towards 3CLpro. Molecular Dynamics simulations indicated a possible interference to the functioning of SARS-CoV-2 targets by the two identified inhibitors. However, further in vitro and in vivo evaluation of these potential SARS-CoV-2 therapeutic inhibitor candidates is needed.
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Affiliation(s)
- Akwasi Boadu
- Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, 4000, South Africa.
- Synthetic and Medicinal Chemistry Research Group (SMCRG), Department of Pharmaceutical Chemistry, Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, 4000, South Africa.
| | - Clement Agoni
- Molecular Bio-Computation and Drug Design Laboratory, School of Health Sciences, Discipline of Pharmaceutical Sciences, University of KwaZulu-Natal, KwaZulu-Natal, South Africa
| | - Rajshekhar Karpoormath
- Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, 4000, South Africa
- Synthetic and Medicinal Chemistry Research Group (SMCRG), Department of Pharmaceutical Chemistry, Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, 4000, South Africa
| | - Mahmoud Soliman
- Molecular Bio-Computation and Drug Design Laboratory, School of Health Sciences, Discipline of Pharmaceutical Sciences, University of KwaZulu-Natal, KwaZulu-Natal, South Africa
| | - Manimbulu Nlooto
- Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, 4000, South Africa
- Department of Pharmacy, School of Health Care Sciences, University of Limpopo, Private Bag X1106, Polokwane, Sovenga, 0727, South Africa
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39
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Kansal N, Garg P, Singh O. Temperature-Based Topological Indices and QSPR Analysis of COVID-19 Drugs. Polycycl Aromat Compd 2022. [DOI: 10.1080/10406638.2022.2086271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Neha Kansal
- Department of Mathematics, University of Rajasthan, Jaipur, Rajasthan, India
| | - Pravin Garg
- Department of Mathematics, University of Rajasthan, Jaipur, Rajasthan, India
| | - Omendra Singh
- Department of Mathematics, University of Rajasthan, Jaipur, Rajasthan, India
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40
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Gyebi GA, Ogunyemi OM, Adefolalu AA, López-Pastor JF, Banegas-Luna AJ, Rodríguez-Martínez A, Pérez-Sánchez H, Adegunloye AP, Ogunro OB, Afolabi SO, Baazeem A, Alotaibi SS, Batiha GES. Antimalarial phytochemicals as potential inhibitors of SARS-CoV-2 guanine N7-methyltransferase (nsp 14): an integrated computational approach. J Biomol Struct Dyn 2022:1-23. [DOI: 10.1080/07391102.2022.2078408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Gideon A. Gyebi
- Department of Biochemistry, Bingham University, Karu, Nigeria
- Natural Products and Structural (Bio-Chem)-Informatics Research Laboratory (NpsBC-Rl), Bingham University, Karu, Nigeria
| | - Oludare M. Ogunyemi
- Human Nutraceuticals and Bioinformatics Research Unit, Department of Biochemistry, Salem University, Lokoja, Nigeria
| | | | - Juan F. López-Pastor
- Structural Bioinformatics and High-Performance Computing Research Group (BIO-HPC), Computer Engineering Department, Universidad Católica de Murcia (UCAM), Murcia, Spain
| | - Antonio J. Banegas-Luna
- Structural Bioinformatics and High-Performance Computing Research Group (BIO-HPC), Computer Engineering Department, Universidad Católica de Murcia (UCAM), Murcia, Spain
| | - Alejandro Rodríguez-Martínez
- Structural Bioinformatics and High-Performance Computing Research Group (BIO-HPC), Computer Engineering Department, Universidad Católica de Murcia (UCAM), Murcia, Spain
| | - Horacio Pérez-Sánchez
- Structural Bioinformatics and High-Performance Computing Research Group (BIO-HPC), Computer Engineering Department, Universidad Católica de Murcia (UCAM), Murcia, Spain
| | | | - Olalekan B. Ogunro
- Department of Biological Sciences, KolaDaisi University, Ibadan, Nigeria
| | - Saheed O. Afolabi
- Faculty of Basic Medical Sciences, Department of Pharmacology and Therapeutics, University of Ilorin, Ilorin, Nigeria
| | - Alaa Baazeem
- Department of Biology, College of Science, Taif University, Taif, Saudi Arabia
| | - Saqer S. Alotaibi
- Department of Biology, College of Science, Taif University, Taif, Saudi Arabia
| | - Gaber El-Saber Batiha
- Faculty of Veterinary Medicine, Department of Pharmacology and Therapeutics, Damanhour University, Damanhour, Egypt
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Treatment of COVID-19 Patients Using Some New Topological Indices. J CHEM-NY 2022. [DOI: 10.1155/2022/7309788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
COVID-19 is causing havoc to human health and the world economy right now. It is a single standard positive-sense RNA virus which is transferred by inhalation of a viral droplet. Its genome forms four structural proteins such as nucleocapsid protein, membrane protein, spike protein, and envelop protein. The capsid of coronavirus is a protein shell within which a positive strand of RNA is present which enables the virus to control the machinery of human cells. It has several variants, e.g., SARS, MERS, and now a new variant identified in 2019, which is a novel coronavirus that causes novel coronavirus disease (COVID-19). COVID-19 is a novel coronavirus disease that originally arose in Wuhan, China, and quickly spread around the world. Clinically, we identified the virus presence by a PCR-based test. Preventive measures and vaccination are the only treatment against coronavirus. Some of these include Remdesivir (GS-5734), Chloroquine, Hydroxychloroquine, and Theaflavin. A topological index (TI) is a mathematical function that assigns a numerical value to a (molecular) graph and predicts many physical, chemical, biological, thermodynamical, and structural features of that network. In this work, we will calculate a new topological index, namely, the first and second Gourava and Hyper-Gourava indices for the molecular graph of Remdesivir (GS-5734), Chloroquine, Hydroxychloroquine, and Theaflavin. We also plotted our computed results to examine how they were affected by the parameters involved. These findings could contribute in the development of new COVID-19 therapy options.
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42
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Bajka A, Toro M, Kniestedt C, Zweifel S. Decrease in Visual Acuity in a 77-Year-old Woman with Age-Related Macular Degeneration after a SARS-CoV-2 Infection Treated with Hydroxychloroquine. Klin Monbl Augenheilkd 2022; 239:527-530. [PMID: 35472798 DOI: 10.1055/a-1766-7035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Anahita Bajka
- Ophthalmology, University Hospital of Zürich, Zürich, Switzerland
| | - Mario Toro
- Ophthalmology, University Hospital of Zürich, Zürich, Switzerland
| | | | - Sandrine Zweifel
- Ophthalmology, University Hospital of Zürich, Zürich, Switzerland
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43
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Osteoarthritis, Corticosteroids and Role of CYP Genes in COVID-19 Patients: A Mini Review. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2022. [DOI: 10.22207/jpam.16.1.28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Objectives of this review is to evaluate the role of cytochrome P450 gene polymorphisms in COVID-19 infected patients with pre-existing OA on corticosteroids. The purpose of this review is to analyze whether polymorphisms of Cytochrome p450 isoforms (CYP2C9 and CYP3A4) affect the dosage of steroids in OA patients in COVID-19 infected patients. This review may provide more therapeutic options; suggest a few guidelines which may be useful in managing COVID-19 patients with pre-existing osteoarthritis. The important role of corticosteroids in treating patients infected with COVID-19 with preexisting osteoarthritis, its influence on incidence of mortality or morbidity may be highlighted. The influence of CYP enzymes and their polymorphisms suggest safety of treatments as well as the possible need for the dosage adjustment or their discontinuation.
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44
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Morgulchik N, Athanasopoulou F, Chu E, Lam Y, Kamaly N. Potential therapeutic approaches for targeted inhibition of inflammatory cytokines following COVID-19 infection-induced cytokine storm. Interface Focus 2022; 12:20210006. [PMID: 34956607 PMCID: PMC8662389 DOI: 10.1098/rsfs.2021.0006] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Accepted: 10/14/2021] [Indexed: 12/15/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) is a deadly respiratory disease caused by severe acute respiratory syndrome coronavirus 2, which has caused a global pandemic since early 2020 and severely threatened people's livelihoods and health. Patients with pre-diagnosed conditions admitted to hospital often develop complications leading to mortality due to acute respiratory distress syndrome (ARDS) and associated multiorgan failure and blood clots. ARDS is associated with a cytokine storm. Cytokine storms arise due to elevated levels of circulating cytokines and are associated with infections. Targeting various pro-inflammatory cytokines in a specific manner can result in a potent therapeutic approach with minimal host collateral damage. Immunoregulatory therapies are now of interest in order to regulate the cytokine storm, and this review will summarize and discuss advances in targeted therapies against cytokine storms induced by COVID-19.
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Affiliation(s)
- Nelli Morgulchik
- Department of Chemistry, Molecular Sciences Research Hub, Imperial College London, London, UK
| | - Foteini Athanasopoulou
- Department of Chemistry, Molecular Sciences Research Hub, Imperial College London, London, UK
| | - Edmund Chu
- Department of Chemistry, Molecular Sciences Research Hub, Imperial College London, London, UK
| | - Yoriko Lam
- Department of Chemistry, Molecular Sciences Research Hub, Imperial College London, London, UK
| | - Nazila Kamaly
- Department of Chemistry, Molecular Sciences Research Hub, Imperial College London, London, UK
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45
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Akhigbe RE, Dutta S, Hamed MA, Ajayi AF, Sengupta P, Ahmad G. Viral Infections and Male Infertility: A Comprehensive Review of the Role of Oxidative Stress. FRONTIERS IN REPRODUCTIVE HEALTH 2022; 4:782915. [PMID: 36303638 PMCID: PMC9580820 DOI: 10.3389/frph.2022.782915] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Accepted: 01/11/2022] [Indexed: 12/16/2022] Open
Abstract
Viral infections have been a part of human existence to date, though viruses have posed a huge threat with various outbreaks lately. These threats are associated with reproductive health challenges, especially male infertility. The prime focus of this review is to highlight the mechanisms associated with viral infection-induced male infertility/subfertility and identify new treatment strategies with the aim to preserve male fertility. The reviewed data showed that viral infections stimulate inflammatory responses, resulting in the release of proinflammatory cytokines, which induces oxidative stress. This oxido-inflammatory cycle could continue in a vicious cycle and threaten male fertility. Existing data from human and experimental studies show that viral infection-induced oxido-inflammatory response results in testicular damage, atrophy of the seminiferous tubules and Sertoli cells, and reduced Leydig cell mass. This is accompanied by reduced circulatory testosterone, impaired spermatogenesis, reduced sperm motility, lipid peroxidation, DNA fragmentation and apoptosis of the sperm cells. Based on the available pieces of evidence, antioxidant therapy, in vivo and in vitro, may be beneficial and protects against the potential risk of male infertility from viral infection. It is, however recommended that more clinical studies be conducted to demonstrate the possible protective roles of antioxidants used as adjuvant therapy in viral infections, and in the in vitro treatment of semen samples for those utilizing semen washing and artificial reproductive techniques.
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Affiliation(s)
- Roland E. Akhigbe
- Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
- Reproductive Biology and Toxicology Research Laboratories, Oasis of Grace Hospital, Osogbo, Nigeria
| | - Sulagna Dutta
- Department of Oral Biology and Biomedical Sciences, Faculty of Dentistry, MAHSA University, Jenjarom, Malaysia
| | - Moses A. Hamed
- Reproductive Biology and Toxicology Research Laboratories, Oasis of Grace Hospital, Osogbo, Nigeria
- Brainwill Laboratories, Osogbo, Nigeria
| | - Ayodeji F. Ajayi
- Department of Physiology, Ladoke Akintola University of Technology, Ogbomoso, Nigeria
| | - Pallav Sengupta
- Department of Physiology, Faculty of Medicine, Biosciences and Nursing, MAHSA University, Jenjarom, Malaysia
- *Correspondence: Pallav Sengupta
| | - Gulfam Ahmad
- Redox Biology Group, Discipline of Pathology, Faculty of Medicine and Health, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia
- Gulfam Ahmad
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Khan MA, Bin Islam S, Rakib MU, Alam D, Hossen MM, Tania M, Asad A. Major Drugs Used in COVID-19 Treatment: Molecular Mechanisms, Validation
and Current Progress in Trials. CORONAVIRUSES 2022; 3. [DOI: 10.2174/2666796701999201204122819] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 11/16/2020] [Accepted: 11/11/2020] [Indexed: 07/28/2024]
Abstract
Background:
Currently, the present world is facing a new deadly challenge against a pandemic disease called
COVID-19, which is caused by a coronavirus, named SARS-CoV-2. To date, there is no drug or vaccine that can treat
COVID-19 completely, but some drugs have been used primarily, and they are in different stages of clinical trials. This
review article discussed and compared those drugs which are running ahead in COVID-19 treatments.
Methods:
We have explored PUBMED, SCOPUS, WEB OF SCIENCE, as well as press release of WHO, NIH and FDA for
articles about COVID-19, and reviewed them.
Results:
Drugs like favipiravir, remdesivir, lopinavir/ritonavir, hydroxychloroquine, azithromycin, ivermectin,
corticosteroids and interferons have been found effective in some extents, and partially approved by FDA and WHO to treat
COVID-19 at different phases of pandemic. However, some of these drugs have been disapproved later, although clinical
trials are going on. In parallel, plasma therapy has been found fruitful in some extents too, and a number of vaccine trails are
going on.
Conclusions:
This review article discussed the epidemiologic and mechanistic characteristics of SARS-CoV-2, and how
drugs could act on this virus with the comparative discussion on progress and backwards of major drugs used till date,
which might be beneficial for choosing therapies against COVID-19 in different countries.
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Affiliation(s)
- Md. Asaduzzaman Khan
- The Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical
University, Luzhou, Sichuan 646000, China
| | - Shad Bin Islam
- Bachelor in Medicine and Surgery Program, Affiliated hospital of Southwest
Medical University, Luzhou, Sichuan 646000, China
| | - Mejbah Uddin Rakib
- Bachelor in Medicine and Surgery Program, Affiliated hospital of Southwest
Medical University, Luzhou, Sichuan 646000, China
| | - Didarul Alam
- Bachelor in Medicine and Surgery Program, Affiliated hospital of Southwest
Medical University, Luzhou, Sichuan 646000, China
| | - Md. Munnaf Hossen
- Department of Immunology, Health Science Center, Shenzhen,
University, Shenzhen, Guangdong 518060, China
| | - Mousumi Tania
- Division of Molecular Cancer, Red Green Research Center,
Dhaka, Bangladesh
| | - Asaduzzaman Asad
- Department of Biochemistry and Molecular Biology, Jahangirnagar University; and International
Center for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh
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Zhen W, Khalid A, Ali P, Rehman H, Siddiqui MK, Ullah H. Topological Study of Some Covid-19 Drugs by Using Temperature Indices. Polycycl Aromat Compd 2022. [DOI: 10.1080/10406638.2022.2025864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Wang Zhen
- School of Computer Engineering, Anhui Wenda University of Information Engineering, Hefei, China
| | - Asma Khalid
- Department of Mathematics, Air University Islamabad, Multan, Pakistan
| | - Parvez Ali
- Department of Mechanical Engineering, College of Engineering, Qassim University, Unaizah, Saudi Arabia
| | - Haider Rehman
- Department of Mathematics, Air University Islamabad, Multan, Pakistan
| | | | - Hameed Ullah
- Department of Mathematics, Comsats University Islamabad, Sahiwal, Pakistan
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Middha SK, David A, Haldar S, Boro H, Panda P, Bajare N, Milesh L, Devaraj V, Usha T. Databases, DrugBank, and virtual screening platforms for therapeutic development. COMPUTATIONAL APPROACHES FOR NOVEL THERAPEUTIC AND DIAGNOSTIC DESIGNING TO MITIGATE SARS-COV-2 INFECTION 2022. [PMCID: PMC9300480 DOI: 10.1016/b978-0-323-91172-6.00021-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
The upsurge of the severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) has turned into a global health disaster. Many remodeled medications were suggested for treatment in the early stages of this pandemic, but these dosages afterward came across with distinct offshoots. Thus, these consequences compelled the scientists to develop new drugs using various antiviral, antiinflammatory, antibacterial, and phytochemical compounds. A handful of drugs have been scrutinized in silico, in vitro, plus through human trials such as anti-SARS-CoV-2 agents and made available as various databases by various scientific communities. The SARS-CoV-2 pandemic databases are designed to allay difficulties associated with this scenario. Some of the popular databases are GESS (global evaluation of SARS-CoV-2/HCoV-19 sequences) which gives a thorough study of data based on tenfold of thousands of complete coverage and quality of SARS-CoV-2 genomes, CORona Drug InTERactions (CORDITE) database for SARS-CoV-2 which profoundly combines the understanding of potential drugs and make it available for scientists and medicos. SARSCOVIDB set one’s sights to merge all differential gene expression data, at mRNA and protein levels, helping to accelerate analysis and research on the molecular impact of covid-19. This chapter aims to provide a piece of complete information about the SARS-CoV-2 virus databases, potentially available drugs, and virtual screening methods. And also provides a different webserver to reach out for information related to the COVID-19 pandemic and its future.
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Ukwenya VO, Adelakun SA, Fuwape TA, Adeagbo AS. The Impact of Deranged Glucose Metabolism and Diabetes in the Pathogenesis and Prognosis of the Novel SARS-CoV-2: A Systematic Review of Literature. Curr Diabetes Rev 2022; 18:e060821195355. [PMID: 34365925 DOI: 10.2174/1573399817666210806104349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 02/28/2021] [Accepted: 03/29/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND The novel coronavirus disease (COVID-19), declared a global pandemic by the World Health Organization (WHO) on March 11, 2020, and has constituted one of the most serious health challenges of the century, globally. The causative organism was initially named the 2019 novel coronavirus (2019 n CoV) but has subsequently been renamed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The pandemic has so far infected several millions and killed about a million people worldwide. Diabetes mellitus (DM) is one of the leading causes of morbidity worldwide. OBJECTIVES To examine the critical role diabetes plays in the pathogenesis and prognosis of COVID-19 and to assess the emerging therapies available to fight the pandemic. METHODS Authors conducted a systematic review of the literature to examine the role of diabetes as comorbidity in the pathogenesis and prognosis of COVID-19 by searching PubMed and Science Direct databases mainly for articles published since the outbreak of the pandemic. RESULTS Both experimental and observational data from early 2020 suggested that most people with COVID-19 have comorbidities, the most dominant of which are diabetes, cardiovascular disease, and hypertension. Empirical evidence indicates that diabetic patients infected with the COVID-19 disease had the worst outcomes concerning morbidity and mortality. CONCLUSION A combination of underlying chronic conditions such as hypertension, obesity, and cardiovascular diseases together with altered ACE receptor expression, immune dysregulation via cytokine storm, alveolar and endothelial dysfunction, increased systemic coagulation may put individuals with diabetes at risk for COVID-19 severity. More studies are needed to elucidate how glucose- lowering drugs may modulate the host immune response in diabetic individuals, especially following the administration of potential COVID-19 vaccines.
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Affiliation(s)
- Victor O Ukwenya
- Department of Human Anatomy, School of Basic Medical Sciences, College of Health Sciences, Federal University of Technology, Akure, Nigeria
| | - Sunday A Adelakun
- Department of Human Anatomy, School of Basic Medical Sciences, College of Health Sciences, Federal University of Technology, Akure, Nigeria
| | - Temiloluwa A Fuwape
- Department of Global and Community Health, College of Health Services, George Mason University, Virginia, VA, USA
| | - Ayotunde S Adeagbo
- Department of Physiology, School of Basic Medical Sciences, College of Health Sciences, Federal University of Technology, Akure, Nigeria
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Masoudi-Sobhanzadeh Y, Esmaeili H, Masoudi-Nejad A. A fuzzy logic-based computational method for the repurposing of drugs against COVID-19. BIOIMPACTS : BI 2022; 12:315-324. [PMID: 35975205 PMCID: PMC9376160 DOI: 10.34172/bi.2021.40] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 03/27/2021] [Accepted: 04/03/2021] [Indexed: 01/09/2023]
Abstract
Introduction: COVID-19 has spread out all around the world and seriously interrupted human activities. Being a newfound disease, not only many aspects of the disease are unknown, but also there is not an effective medication to cure the disease. Besides, designing a drug is a time-consuming process and needs large investment. Hence, drug repurposing techniques, employed to discover the hidden benefits of the existing drugs, maybe a useful option for treating COVID-19. Methods: The present study exploits the drug repositioning concepts and introduces some candidate drugs which may be effective in controlling COVID-19. The suggested method consists of three main steps. First, the required data such as the amino acid sequences of targets and drug-target interactions are extracted from the public databases. Second, the similarity score between the targets (protein/enzymes) and genome of SARS-COV-2 is computed using the proposed fuzzy logic-based method. Since the classical approaches yield outcomes which may not be useful for the real-world applications, the fuzzy technique can address the issue. Third, after ranking targets based on the obtained scores, the usefulness of drugs affecting them is examined for managing COVID-19. Results: The results indicate that antiviral medicines, designed for curing hepatitis C, may also cure COVID-19. According to the findings, ribavirin, simeprevir, danoprevir, and XTL-6865 may be helpful in controlling the disease. Conclusion: It can be concluded that the similarity-based drug repurposing techniques may be the most suitable option for managing emerging diseases such as COVID-19 and can be applied to a wide range of data. Also, fuzzy logic-based scoring methods can produce outcomes which are more consistent with the real-world biological applications than others.
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Affiliation(s)
- Yosef Masoudi-Sobhanzadeh
- Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
,Corresponding authors: Ali Masoudi-Nejad, ; Yosef Masoudi-Sobhanzadeh,
| | - Hosein Esmaeili
- Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
| | - Ali Masoudi-Nejad
- Laboratory of Systems Biology and Bioinformatics (LBB), Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
,Corresponding authors: Ali Masoudi-Nejad, ; Yosef Masoudi-Sobhanzadeh,
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