Table 1.
The potential repurposing drugs under investigation for the treatment of COVID-19 infection. AMPK, Adenosine monophosphate–activated protein kinase; AT1, Angiotensin 1; mTOR, mechanistic target of rapamycin; IL, interleukin; Nrf2, nuclear factor erythroid 2 (NFE2)–related factor 2; SIRT1, silent mating–type information regulation 2 homolog 1; TNF, tumor necrosis factor; TMPRSS2, active transmembrane serine protease 2
| S. No | Drug | Drug target | Summary | Ref |
|---|---|---|---|---|
| 1 | Camostat mesilate | TMPRSS2 | Camostat mesilate inhibits TMPRSS2 and blocks COVID-19 infection in cultures of human Caco-2 and simian Vero E6 cells | [96] |
| 2 | Nafamostat mesilate | TMPRSS2 | Inhibits SARS-CoV-2 infection of Vero cells by blocking TMPRSS2 glycoprotein | [97] |
| 3 | Recombinant human Angiotensin II peptide | Angiotensin II | La Jolla Pharmaceutical’s Giapreza Company has repurposed this drug for COVID-19 infection which previously used to control blood pressure | [98] |
| 4 | Valsartan | AT1 receptor | Novartis repurposed this drug for COVID-19 infection and under phase 4 clinical trials which previously approved for the treatment of hypertension | [99] |
| 5 | Sirolimus | mTOR | Sirolimus is repurposed by Pfizer company for COVID-19 infection which is under phase 2 clinical trials by blocking mTOR in turn induces autophagy. This drug was previously approved for the treatment of organ rejection | [100] |
| 6 | Dimethyl fumarate and 4-octyl itaconate | Nrf2 | Blocked the inflammatory response to SARS-CoV2 in human cells, including peripheral blood mononuclear cells (PBMCs) from COVID-19 patients | [86] |
| 7 | Tocilizumab | IL-6 receptor | A humanized monoclonal antibody against the IL-6 receptor is being studied and repurposed against COVID-19 patients | [101] |
| 8 | Anakinra | IL-1 receptor | A recombinant human IL-1 receptor antagonist is repurposed and studied against COVID-19 patients | [102] |
| 9 | Metformin | AMPK | Studies reported that the risk of deaths in diabetics with COVID-19 infection was significantly less when compared to the patients without metformin therapy, so it would be demonstrated as a potential drug in managing COVID-19 infection | [103] |
| 10 | Bardoxolone methyl | Nrf2 | Registered in clinical trials with title “BARCONA: A phase II/III, randomized, double-blind, placebo-controlled, multi-center study of the effects of bardoxolone methyl in participants with SARS-Corona Virus-2 (COVID-19)”, to study the effects of bardoxolone methyl in COVID-19 infected patients | NCT04494646 |
| 11 | Resveratrol | SIRT1 | Registered in clinical trials with title “Randomized proof-of-concept trial to evaluate the safety and explore the effectiveness of resveratrol for COVID-19”, which was a phase II clinical trial | NCT04400890 |
| 12 | Mitochondrial genes | Mitochondria in patient blood samples | In this study, they collected the blood samples from COVID-19-infected patients who have a previous history of mitochondrial diseases and correlate these mitochondrial genes with severity in COVID-19 infection | NCT04419870 |
| 13 | Infliximab | TNFα | A prospective, single-center, phase 2 trial is proposed to assess the efficacy of infliximab or infliximab-abda in hospitalized adult patients with severe or critical COVID-19 patients by blocking TNFα | NCT04425538 |
| 14 | Isotretinoin | ACE2 | Inhibits ACE2 which was registered for phase III clinical trials studying against COVID-19 infection in patients | NCT04361422 |
| 15 | Silymarin | Oxidative stress | A randomized placebo-controlled trial to assess the clinical outcome in COVID-19 pneumonia following administration of silymarin owing to its role as a p38 MAPK pathway inhibitor and its antiviral, anti-inflammatory and antioxidant effects | NCT04394208 |
| 16 | Hesperidin and diosmin mixture | Oxidative stress | Early phase I trial intended to find antiviral activity of hesperidin by targeting oxidative stress and inflammation associated with COVID-19 infection in patients. Hesperidin mixture with diosmin co-administrated with heparin protect against venous thromboembolism which may prevent disease progression | NCT04452799 |
| 17 | Ascorbic acid | Oxidative stress and inflammation | This is a single-center, prospective, randomized, open-label, phase II clinical trial designed to assess the efficacy, tolerability, and safety of pharmacologic AA administration in hospitalized patients newly diagnosed with COVID-19 who will likely not require mechanical ventilation within 24 h of the study intervention | NCT04363216 |
| 18 | Quercetin | Oxidative stress and inflammation | The aim of this study is to evaluate the possible role of quercetin on prophylaxis and treatment of COVID-19 infection in patients by targeting oxidative stress and inflammation | NCT04377789 |