Emerging therapeutics in the management of COVID-19

Table 1 Monoclonal antibodies (a survey)

Drug	Current use/FDA approval	Proposed mechanism of action	Published trials
Sarilumab	FDA approved for use in rheumatoid arthritis	Monoclonal antibody, IL-6 receptor antagonist	(1) Sanofi and Regeneron [10]; (2) Benucci et al[11]; and (3) See Clinicaltrials.gov for ongoing trials
Siltuximab	FDA Approved for use in Multicentric Castleman’s disease	Monoclonal antibody, IL-6 receptor antagonist	(1) Gritti et al[14]; and (2) See Clinicaltrials.gov for ongoing trials
Leronlimab	Not currently FDA approved, however under investigation for COVID-19 and HIV	Monoclonal antibody, CCR5 antagonist	(1) CytoDyn [17]; and (2) See Clinicaltrials.gov for ongoing trials
PD-1 inhibitors	FDA approved for the treatment of various malignancies	Inhibition of PD-1 pathway	No currently published trials
Gimsilumab	Not currently FDA approved. Clinical Trials are underway testing Gimsilumab as a treatment for ankylosing spondylitis as well as ARDS	Monoclonal antibody against GM-CSF	See Clinicaltrials.gov for ongoing trials

FDA: Federal Drug Administration; IL: Interleukin; COVID-19: Coronavirus disease 2019; HIV: Human immunodeficiency virus; PD-1: Programmed cell death protein 1; GM-CSF: Granulocyte macrophage colony stimulating factor; ARDS: Acute respiratory distress syndrome.

Table 2 Antivirals (a survey)

Drug	Current use/FDA approval	Proposed mechanism of action	Published trials
Arbidol	Approved in other countries for influenza treatment and prophylaxis, however not approved in the United States	Antiviral, inhibits viral-mediated fusion with target membrane, blocking viral entry into target cells	Zhang et al[38]
ASC09	Not currently FDA approved. Trials are underway testing ASC09 as a treatment for HIV and COVID-19	Antiviral, Protease inhibitor	See Clinicaltrials.gov for ongoing trials
Azvudine	Currently being tested in clinical trials for HIB and COVID-19	Antiviral, nucleoside reverse transcriptase inhibitor	See Clinicaltrials.gov for ongoing trials
Favipravir	Approved in other countries for the treatment of influenza, however not FDA approved in the United States	Antiviral, Inhibits RNA-dependent RNA polymerase	(1) Cai et al[52]; (2) Chen et al[33]; and (3) See Clinicaltrials.gov for ongoing trials
Baloxavir marboxil	Approved for treatment of uncomplicated influenza A and B in individuals age 12 and older who have been symptoms for no more than 48 h	Antiviral, cap-dependent endonuclease inhibitor	Lou et al[59]
Remdesivir	FDA Emergency Use Authorization for COVID-19	Antiviral, inhibitor of RNA-dependent RNA polymerase	(1) Wang et al[68]; (2) NIH (ACTT trial)[69]; (3) Beigel et al[71]; and (4) See Clinicaltrials.gov for ongoing trials

FDA: Federal Drug Administration; COVID-19: Coronavirus disease 2019; HIV: Human immunodeficiency virus; NIH: National Institutes of Health; ACTT: Adaptive COVID-19 Treatment Trial.

Table 3 Cell and RNA-based therapies

Drug	Current use/FDA approval	Proposed mechanism of action	Published trials
Mesenchymal stem cells	FDA approved for graft versus host disease	Prevention of cytokine release as well as promotion of cellular repair/regeneration	(1) Leng et al[75]; and (2) See Clinicaltrials.gov for ongoing trials
MultiStem	Currently being studied for treatment of ischemic stroke, ulcerative colitis, acute myocardial infarction, and graft vs host disease	Immune system modulation, anti-inflammatory, pro-angiogenic	See Clinicaltrials.gov for ongoing trials
RNA based therapies	Have been utilized as anticancer and antiviral therapy. Have also been implemented in genetic diseases	Interfere with gene expression through RNA interference	See Clinicaltrials.gov for ongoing trials

FDA: Federal Drug Administration.

Table 4 Miscellaneous therapeutics

Drug	Current use/FDA approval	Proposed mechanism of action	Published trials
APN01	Known to have anti-hypertensive and anti-neoplastic properties	Cleaves angiotensin II to form angiotensin-1-7	See Clinicaltrials.gov for ongoing trials
Chloroquine/hydroxychloroquine	Anti-malarial, anti-viral, and anti-rheumatic effects. Previous studied in the 2004 SARS outbreak	Poorly understood. Likely mechanism includes accumulation of basic drug in lysosomes, altering pH and disrupting enzymes involved in post-translation protein modification	(1) Gautret et al[105]; (2) Tang et al[107]; (3) Borba et al[108]; (4) Horby et al[109]; and (5) Boulware et al[110]
Azithromycin	Macrolide antibiotic, classically using in the treatment of several bacterial infectious processes	Bacteriostatic properties due to binding of the 50 s ribosomal subunit, inhibiting bacterial protein synthesis. Against SARS-CoV-2, it is hypothesized that intracellular accumulation alters pH, leading to interference with viral activities	(1) All trials have been performed using Azithromycin as an adjunct to CQ/HCQ; and (2) No clinical trials evaluating the efficacy of azithromycin alone
Colchicine	Treatment for gout. Implicated in familial Mediterranean fever, primary biliary cirrhosis, psoriasis, sarcoidosis, scleroderma, amyloidosis, pericarditis, Sweet syndrome, and Behcet disease	Anti-inflammatory agent, binds to beta-tubulin in neutrophils leading to inhibition of assembly and polymerization of microtubules. This leads to decrease in several neutrophilic inflammatory processes	Gendelman et al[123]
Corticosteroids/methylprednisolone	Used in a variety of clinical instances as anti-inflammatory agents	Extensive anti-inflammatory and anti-fibrotic properties, thought to decrease inflammation	(1) Wu et al[135]; (2) Wang et al[133]; and (3) Horby et al[136]
Ivermectin	Used as an anti-parasitic agent, however has shown antiviral activity against numerous pathogens	May play a role in inhibiting viral nuclear import into the host cell via interactions with IMPalpha/B1	Caly et al[143]
Convalescent plasma	Has been used in previous pandemics, including SARS, MERS, Ebola, and H1N1 for the purpose of passive immunization	By sharing plasma of individuals who have previously been infected, passive immunization occurs	(1) Li et al[148]; (2) Shen et al[149]; and (3) Duan et al[150]
ECMO	Used to support cardiac and pulmonary function in critically ill patients	Assists the cardiorespiratory system functioning in patients with severe ARDS	Currently, no randomized clinical trials have evaluated the efficacy of using ECMO in the treatment of COVID-19

FDA: Federal Drug Administration; COVID-19: Coronavirus disease 2019; SARS: Severe acute respiratory syndrome; ECMO: Extracorporeal membrane oxygenation; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; ARDS: Acute respiratory distress syndrome; CQ: Chloroquine; HCQ: Hydroxychloroquine.