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Table 3 FDA approved drugs/therapies which can likely target SARS-CoV-2 life cycle and/or COVID-19 complications (see also, Table 1)

From: Insights to SARS-CoV-2 life cycle, pathophysiology, and rationalized treatments that target COVID-19 clinical complications

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 [172, 173]
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 [174,175,176]
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 [174,175,176]
Homoharringtonine (Omacetaxine) Protein translation inhibitor Chronic myeloid leukemia Reduces SARS-CoV-2 pseudoviral entry, in vitro Myelosuppression [177,178,179,180]
Verteporfin Photosensitizer for photodynamic therapy Subfoveal choroidal neovascularisation Reduces SARS-CoV-2 pseudoviral entry, in vitro Visual disturbances [177,178,179,180]
Cilnidipine Calcium channel blocker Hypertension Reduces SARS-CoV-2 pseudoviral entry, in vitro None reported [177,178,179,180]
Dasatinib Tyrosine kinase inhibitor Chronic myeloid leukemia,
acute lymphoblastic leukemia
Reduces SARS-CoV-2 pseudoviral entry, in vitro Cytopenia, pleural effusion [177,178,179,180]
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 [177,178,179,180]
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 [181, 182]
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 [183, 184]
Chlorpromazine Antipsychotic Schizophrenia, bipolar disorders In vitro inhibition of viral replication of coronaviruses Parkinsonism, hypotension [185, 186]
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 see text, [184, 192]
Cathepsin L inhibitor
Teicoplanin Antibacterial Gram positive bacteria (methicillin-resistant Staphylococcus aureus, Enterococcus faecalis) Inhibits SARS Cov-2 replication cycle in vitro None reported [190, 193]
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 [195, 196]
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 [200,201,202,203]
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 [200,201,202,203]