Table 1.
Drugs currently in trials to treat COVID-19
| Category | Drug name [Reference] | Route | Mechanism of action | Indications, recommendations | Side effects | Precaution | Comments (Clinical trial no.) |
|---|---|---|---|---|---|---|---|
| Antimalarials and amebicides | Hydroxychloroquine phosphate [[35], [36], [37]] | Oral | Inhibits autophagy and lysosomal acidification. Prevents virus entry in vitro. | Moderate to severe | QT prolongation, headache, nausea, loss of appetite, vomiting, diarrhoea, rash | G6PD deficiency, hearing problems, kidney, liver diseases, diabetes (low blood glucose), porphyria, seizures, psoriasis, cardiomyopathy | FDA EUA approved to treat adults and adolescents for COVID-19 admitted in hospitals. (ChiCTR2000029559) |
| Antimalarials | Chloroquine [35,37,38] | Oral | Not fully understood. Inhibition of viral fusion. Binds and inhibits glycosylation of virus proteins. | Moderate to severe | QT prolongation, headache, nausea, vomiting | G6PD deficiency, hypersensitivity to chloroquine, retinal and visual changes | Considered as part of investigation protocol for patients with COVID-19 infection. (NCT04333628) |
| Antibiotic | Azithromycin [39,40] | Oral | Azithromycin acts by binding to 50S ribosomal subunit of susceptible microorganisms. | Moderate to severe | QT prolongation, headache, dizziness, cholestasis, hepatitis, diarrhoea | Azithromycin is CYP3A4 (it interacts with >200 drugs) | Currently being investigated in clinical trials and also available through expanded access and compassionate use mechanisms for certain patients with COVID-19. (IRCT20200415047092N1) |
| Antiviral agent | Remdesivir [41,42] | Intravenous | Inhibits RdRp of RNA viruses. | Mild to moderate | Elevated liver enzymes, diarrhoea, hypotension, acute kidney injury, atrial fibrillation, deep venous thrombosis | Interacts with clarithromycin and rifampin | Prevents MERS coronavirus disease in monkeys; undergoing clinical trials in China, United States and United Kingdom as potential drug in treating COVID-19. (NCT04365725) |
| Antiviral agent | Favipiravir [43,44] | Oral | Inhibits RdRp of RNA viruses. It is an inhibitor of viral RNA-dependent RNA polymerase, causing chain termination and preventing RNA elongation. | Early to mild | Nausea, vomiting, liver dysfunction | Drug interaction, pregnancy | Approved for treating influenza in Asia. (NCT04358549) |
| HIV protease inhibitor | Lopinavir/ritonavir [45] (Ritonavir is combined with lopinavir to increase its plasma half-life through the inhibition of cytochrome P450) | Oral | Aspartate protease inhibitor. Lopinavir binds to site of HIV-1 protease activity and inhibits cleavage of virus Gag-Pol polyprotein precursors, hence interfering with HIV infection. | Moderate to severe | Anorexia, nausea, abdominal discomfort, diarrhoea, acute gastritis, liver dysfunction, thrombocytopenia, skin eruptions | Drug interactions (it is a CYP3A4 substrate) | No benefit observed with lopinavir/ritonavir treatment beyond standard care. (NCT04307693) |
| Antiprotozoal agent | Nitazoxanide [46] | Oral | Disturbs metabolism in anaerobic microbes and inhibits viral transcription factor. | Moderate to severe | Nausea, vomiting, abdominal pain, headache, dizziness, skin rash | Hypersensitivity to nitazoxanide | Nitazoxanide/azithromycin has been tried in combination to treat COVID-19; clinical trial with hydroxychloroquine vs. nitazoxanide is currently being investigated. (NCT04361318, NCT04360356, NCT04343248, NCT04351347, NCT04348409, NCT04341493) |
| Immunomodulator (monoclonal antibody) | Tocilizumab [47] | Intravenous | Monoclonal antibody; blocks IL-6 receptor and inhibit IL-6 pathway. | Severe | Nasopharyngitis, headache, hypertension, elevated alanine aminotransferase, rash, dizziness, leukopenia, liver injury | Thrombocytopenia, neutropenia, acute liver injury, renal failure | Considered as part of an investigation protocol for patients with COVID-19 infection. (NCT04356937) |
| Immunomodulator (monoclonal antibody) | Sarilumab [43] | Subcutaneous | Monoclonal antibody that blocks IL-6 receptor and inhibit IL-6 pathway. | Moderate to severe | Allergy, thrombocytopenia neutropenia, elevated liver transaminases | Allergy to sarilumab, platelets <15 000/m³, elevated alanine transaminases >5 times upper normal limit | Clinical trial of patients with COVID-19 complicated by pneumonia requiring ventilatory support. (NCT04359901, NCT04357808) |
| Immunomodulator (monoclonal antibody) | Siltuximab [48,49] | Intravenous (infusion) | Chimeric monoclonal antibody that binds to and blocks IL-6 effects. | Moderate to severe | Elevation of liver transaminases, thrombocytopenia, skin rash, itching, sweating | Raised liver transaminases and liver dysfunction | Clinical trial of patients with COVID-19 complicated by pneumonia requiring ventilatory support. (NCT04329650) |
| Plasma, neutralizing antibodies | Convalescent plasma [50] | Intravenous | Convalescent plasma contains specific IgG and IgM anti–SARS-CoV-2 antibodies, which can neutralize virus. | Severe and life-threatening | Anaphylaxis | Donors must be screened for transmittable pathogens | FDA outlined requirements that individuals must meet to donate blood for this research. (NCT04333355, NCT04340050, NCT04353206, NCT04343261, NCT04347681, NCT04356482) |
COVID-19, coronavirus disease 2019; CYP3A4, cytochrome P450 family 3 subfamily A member 4; EUA, emergency use authorization; FDA, US Food and Drug Administration; G6PD, glucose-6-phosphate dehydrogenase; IL, interleukin; IL, interleukin; MERS, Middle East respiratory syndrome; RNA-dependent RNA polymerase RdRp; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.