Emerging therapeutics in the management of COVID-19

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.