Abstract
A novel coronavirus known as severe acute respiratory syndrome is rapidly spreading worldwide. The international health authorities are putting all their efforts on quick diagnosis and placing the patients in quarantine. Although different vaccines have come for quick use as prophylactics, drug repurposing seems to be of paramount importance because of inefficient therapeutic options and clinical trial limitations. Here, we used structure-based drug designing approach to find and check the efficacy of the possible drug that can inhibit coronavirus main protease which is involved in polypeptide processing to functional protein. We performed virtual screening, molecular docking and molecular dynamics simulations of the FDA-approved drugs against the main protease of SARS-CoV-2. Using well-defined computational methods, we identified amprenavir, cefoperazone, riboflavin, diosmin, nadide and troxerutin approved for human therapeutic uses, as COVID-19 main protease inhibitors. These drugs bind to the SARS-CoV-2 main protease conserved residues of substrate-binding pocket and formed a remarkable number of non-covalent interactions. We have found diosmin as an inhibitor which binds covalently to the COVID-19 main protease. This study provides enough evidences for therapeutic use of these drugs in controlling COVID-19 after experimental validation and clinical demonstration.
Keywords: Coronavirus; Drug repurposing; Inhibitors; Protease.
【저자키워드】 Drug repurposing, coronavirus, protease, inhibitors, 【초록키워드】 COVID-19, Drug repurposing, SARS-CoV-2, Efficacy, Vaccine, coronavirus, clinical trial, quarantine, Diagnosis, molecular docking, Virtual screening, drug, molecular dynamics, protease, FDA-approved drugs, inhibitors, SARS-CoV-2 main protease, protease inhibitors, Molecular dynamics simulation, Novel coronavirus, Computational methods, Severe acute respiratory syndrome, International, therapeutic, respiratory, inhibitor, interactions, Evidence, Riboflavin, international health, therapeutic option, Amprenavir, Health authority, Diosmin, acute respiratory syndrome, Cefoperazone, troxerutin, nadide, FDA-approved drug, experimental validation, residue, effort, therapeutic use, residues, functional protein, limitations, approach, bind, performed, conserved, involved, the patient, inhibit, approved, provide, inefficient, the SARS-CoV-2, 【제목키워드】 COVID-19, molecular docking, repurposing, FDA-approved drug, approach,