Table 1.
COVID-19 candidate therapeutics with highest potential to be available and easily administrable in the near future
| Candidate therapeutic | Therapeutic class | Examples of current uses | Rationale/mechanism of action | Limitations/potential obstacles | Trials in U.S. National Library of Medicine | Trials in European Union Clinical Trials Register | Trials in WHO International Clinical Trials Registry Platform | |||
|---|---|---|---|---|---|---|---|---|---|---|
| Listed | Completed | Listed | Completed | Listed | Phase 4 | |||||
| Azithromycin | Macrolide antibiotic | Community-acquired pneumonia | Alkalinization of endosomal vesicles/lysozomes, potentially inhibiting endocytosis and/or uncoating of enveloped viruses | No RCTs completed to date except with HCQ/CQ, where it was not shown to be helpful and some signal for harm | 126 | 28 | 27 | 0 | 115 | 4 |
| Baricitinib | JAK1/JAK2 inhibitor | Rheumatoid arthritis | May inhibit viral entry via clathrin-dependent endocytosis; immunomodulator | May have cost and availability issues as IP owned by Eli Lilly | 18 | 2 | 11 | 1 | 16 | 2 |
| Camostat | Serine protease inhibition | Chronic pancreatitis | TMPRSS2 inhibitor | Trials pending | 25 | 1 | 6 | 0 | 26 | 1 |
| CQ | Antimalarial | Malaria, autoimmune conditions, rheumatologic diseases | Block viral entry (see HCQ); immunomodulator | More toxicity than HCQ with less preclinical evidence of antiviral activity; negative clinical trial | 91 | 20 | 11 | 0 | 49 | 13 |
| HCQ | Antimalarial | Malaria, autoimmune conditions, rheumatologic diseases | Block viral entry by impairing terminal glycosylation of ACE2 receptors, proteolytic processing, and endosomal acidification; immunomodulator |
Multiple negative trials in all phases of illness, from pre-exposure prophylaxis to treatment of hospitalized patients | 274 | 64 | 70 | 2 | 382 | 33 |
| Colchicine | Antiinflam. | Gout, Behcet disease | Reduce neutrophil chemotaxis, cytokine production, IL-1beta | Narrow therapeutic index | 32 | 5 | 8 | 1 | 46 | 0 |
| Favipiravir | Antiviral | Investigations for Nipah virus, Ebola, and other flaviviruses | RNA-dependent RNA polymerase inhibition | Safety concerns regarding increases in blood uric acid and teratogenic potential | 52 | 13 | 9 | 0 | 67 | 3 |
| IFN | Biologic response modifier | Hepatitis C, multiple sclerosis | Strengthens IFN response to SARS-CoV-2 infection | Subcutaneous administration (though nasal administration possible); large negative trial | 147 | 12 | 20 | 0 | 99 | 10 |
| Ivermectin | Antiparasitic | Onchocerciasis, lymphatic filariasis, soil-transmitted helminths, scabies | Nuclear transport inhibition | May be difficult to achieve therapeutic dose | 65 | 21 | 6 | 1 | 91 | 6 |
| Lopinavir/ ritonavir | Antiviral | HIV (older regimen) | Protease inhibition | Large negative trial | 92 | 18 | 21 | 0 | 136 | 15 |
| Molnupiravir (formerly MK-4482 and EIDD-2801) | Antiviral | Developed for influenza, investigated for SARS, MERS | Nucleoside analogue | Early-phase trials; may have cost and availability issues as IP owned by Ridgeback; possible mutagenicity (disputed) | 6 | 2 | 0 | 0 | 10 | 0 |
| Niclosamide | Antiparasitic | Tapeworm infections | Inhibits viral entry by change in endosomal pH; inhibit autophagy | Trials few in number and in early stages | 13 | 0 | 2 | 0 | 12 | 2 |
| Nitazoxanide | Antiparasitic | Cryptosporidiosis, broad-spectrum antiparasitic | Phosphorylation of protein kinase activated by dsRNA; immunomodulator | Trials in early stages | 26 | 6 | 0 | 0 | 28 | 4 |
| Ruxolitinib | JAK1/2 kinase inhibitor | Myelofibrosis, polycythemia vera, acute graft-versus-host disease | Potentially inhibits AAK1, and prevents clathrin-mediated viral endocytosis; antiinflam. agent for cytokine storm | Not as potent AAK1 inhibitor as baricitinib | 16 | 1 | 9 | 1 | 24 | 0 |
| Sofosbuvir with daclatasvir or ledipasvir | Antiviral | Hepatitis C | RNA polymerase inhibition | Concerns regarding partial treatment of undiagnosed hepatitis C virus | 12 | 3 | 0 | 0 | 22 | 2 |
| Tofacitinib | JAK1/2 kinase inhibitor | Autoimmune diseases including rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis | Antiinflam. agent for cytokine storm | No detectable inhibition of AAK1 | 6 | 1 | 3 | 0 | 5 | 0 |
| Totals | 1,001 | 197 | 203 | 6 | 1,128 | 95 | ||||
Antiinflam. = antiinflammatory; CQ, chloroquine; HCQ, hydroxychloroquine; IFN = Interferon; IL = interleukin; IP = intellectual property; MERS = Middle East respiratory syndrome; N/A = not available; PCR = polymerase chain reaction; RCT = randomized controlled trial; SARS = severe acute respiratory syndrome.