Table 3 FDA approved drugs/therapies which can likely target SARS-CoV-2 life cycle and/or COVID-19 complications (see also, Table 1)
Intervention | Drug category | Approved indication | Biologic and/or clinical efficacy | Serious adverse events | References |
|---|---|---|---|---|---|
Suppression of ACE2 gene expression | |||||
Dutasteride | 5-a reductase inhibitors | Benign prostate hyperplasia | Reduces ACE2 and inhibits internalization of SARS-Cov-2 S protein in vitro | None reported | |
Anti-TNF agents | Monoclonal antibodies | Autoimmune diseases | Lower incidence of COVID-19 disease in patients with Inflammatory Bowel Disease (Retrospective cohort study and SECURE-IBD database) | Serious infections, demyelinating disorders, drug-induced lupus, may increase risk of malignancies | |
Suppression of TMPRSS2 gene expression | |||||
Anti-TNF agents | Monoclonal antibodies | Autoimmune diseases | Lower incidence of COVID-19 disease in patients with Inflammatory Bowel Disease (Retrospective cohort study and SECURE-IBD database) | Serious infections, demyelinating disorders, drug-induced lupus, may increase risk of malignancies | |
Homoharringtonine (Omacetaxine) | Protein translation inhibitor | Chronic myeloid leukemia | Reduces SARS-CoV-2 pseudoviral entry, in vitro | Myelosuppression | |
Verteporfin | Photosensitizer for photodynamic therapy | Subfoveal choroidal neovascularisation | Reduces SARS-CoV-2 pseudoviral entry, in vitro | Visual disturbances | |
Cilnidipine | Calcium channel blocker | Hypertension | Reduces SARS-CoV-2 pseudoviral entry, in vitro | None reported | |
Dasatinib | Tyrosine kinase inhibitor | Chronic myeloid leukemia, acute lymphoblastic leukemia | Reduces SARS-CoV-2 pseudoviral entry, in vitro | Cytopenia, pleural effusion | |
Venetoclax | Selective BCL-2 inhibitor | Chronic lymphocytic leukemia, small lymphocytic lymphoma | Reduces SARS-CoV-2 pseudoviral entry, in vitro | Neutropenia, lymphopenia, reactivation of hepatitis B, interaction with CYP3A inhibitors and azithromycin | |
Inhibition of TMRPSS2 protease | |||||
Nafamostat mesylate | Serine protease inhibitor | Pancreatitis, anticoagulant during extracorporeal circulation supportive treatment | Inhibits SARS-CoV-2 S-mediated entry into host cells, in vitro | Bleeding | |
Inhibition of clathrin-mediated endocytosis | |||||
Umifenovir | Antiviral | Influenza A and B | Its combination with lopinavir/ritonavir ends to better outcome in COVID-19 patients versus only lopinavir/ritonavir | Hepatotoxicity in combination with lopinavir/ritonavir | |
Chlorpromazine | Antipsychotic | Schizophrenia, bipolar disorders | In vitro inhibition of viral replication of coronaviruses | Parkinsonism, hypotension | |
Inhibition of virus’ main protease | |||||
Glecaprevir | Antiviral | Hepatitis C | Binds with high affinity to SARS-CoV-2 main protease and inhibits it, in vitro | None reported | [187] |
Maraviroc | Antiviral | Human Immunodeficiency Virus | Binds with high affinity to SARS-CoV-2 main protease and inhibits it, in vitro | None reported | [187] |
Inhibition of virus’ RNA-dependent RNA polymerase (RdRp) | |||||
Ribavirin | Antiviral | Respiratory Syncytial Virus infection, Hepatitis C, some viral hemorrhagic fevers | Bind to the SARS-CoV-2 RdRp tightly in vitro, suppressing its function | Neutropenia, thrombocytopenia, neuropsychiatric toxicity | see text, [188] |
Remdesivir | Antiviral | Broad-spectrum antiviral medication | Bind to the SARS-CoV-2 RdRp tightly in vitro, contradicting its function | Hepatotoxicity, nephrotoxicity | see text, [184] |
Sofosbuvir | Antiviral | Hepatitis C | Bind to the SARS-CoV-2 RdRp tightly in vitro, contradicting its function | None reported | see text |
Galidesivir | Antiviral | Hepatitis C | Bind to the SARS-CoV-2 RdRp tightly in vitro, contradicting its function | None reported | see text, [184] |
Tenofovir | Antiviral | Hepatitis B, Human Immunodeficiency Virus | Bind to the SARS-CoV-2 RdRp tightly in vitro, contradicting its function | Renal and bone toxicity | see text, [189] |
Favipiravir | Antiviral | Influenza | Increases clinical recovery over 7 days and reduces fever, cough, and respiratory problems in COVID-19 patients | Teratogenicity, embryotoxicity | [190] |
Inhibition of tubulin polymerization | |||||
Colchicine | Anti-inflammatory | Gout, rheumatic diseases, pericarditis | Improves time to clinical deterioration in COVID-19 patients | Diarrhea | see text, [191] |
Inhibition of the endosomal/lysosomal compartments | |||||
Chloroquine Hydroxychloroquine | Anti-malarial | Malaria, lupus erythematosus, rheumatoid arthritis | COVID-19 load reduction/disappearance with hydroxychloroquine | Cardiac arrest, retinotoxicity | |
Cathepsin L inhibitor | |||||
Teicoplanin | Antibacterial | Gram positive bacteria (methicillin-resistant Staphylococcus aureus, Enterococcus faecalis) | Inhibits SARS Cov-2 replication cycle in vitro | None reported | |
Antioxidants | |||||
Thymoquinone Egcg Vit D3 | Nutritional supplements | Oxidative stress, vitamin deficiency | Combination of the 3 compounds may prevent and/or decrease SARS-CoV-2 infection severity through activation of Nrf2 transcription factor | None reported | [194] |
Zinc | Nutritional supplement | Oxidative stress, zinc deficiency | Clinical improvement in COVID-19 patients | None reported | |
Free radical scavenger | |||||
Ergothioneine | Nutritional supplement | Oxidative stress | Potential reduction of severity and mortality of COVID-19 disease | None reported | [197] |
Immunotherapies to mitigate “cytokine storm” | |||||
Tocilizumab | IL-6 receptor blocking monoclonal antibody | Connective tissue diseases | Rapid improvement in clinical and laboratory measures of hyperinflammation in hospitalized patients with COVID-19 Reduce the risk of invasive mechanical ventilation or death in patients with severe COVID-19 pneumonia | Neutropenia, thrombocytopenia | [198] |
Sarilumab | IL-6 receptor blocking monoclonal antibody | Rheumatoid arthritis | Rapid improvement in respiratory function and normalization of inflammatory markers | Neutropenia, thrombocytopenia, upper respiratory and urinary tract infection | [199] |
Dexamethasone | Corticosteroid | Variety of medical uses | Increase in the number of ventilator-free days in COVID-19 patients with ARDS | Acne, insomnia, vertigo, increased appetite, weight gain, depression | [161] |
Angiotensin converting enzyme (ACE) inhibitors and angiotensin II type 1 receptor (AT2R1) blockers | |||||
ACE inhibitors | Anti-hypertensives | Hypertension | Reduce risk of 28-day death among hospitalized COVID-19 patients with coexisting hypertension and coronary artery disease Decrease the mortality of COVID-19 | Angioedema, anemia | |
AT1R blockers | Anti-hypertensives | Hypertension | Decrease mortality in COVID-19 patients with hypertension | Angioneurotic edema, anemia, liver damage, renal failure, aggravation of angina and migraine | |