Repurposing drug molecule against SARS-Cov-2 (COVID-19) through molecular docking and dynamics: a quick approach to pick FDA-approved drugs

Abstract

Graphical 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. Supplementary Information The online version contains supplementary material available at 10.1007/s00894-021-04923-w.

Relationship Between Phylogenetic of Apium and Foeniculum Plants from Central Java, Indonesia, and Their Secondary Metabolites Potency against COVID-19 Protease

“…This was followed by Cys145 and His163 [38] as we also can observe in the riboflavin interaction residues. In addition, Gly143 and Glu166 reported playing an important role in stabilizing the ligand-receptor complex [39].…”

Cheminformatics Bioprospection of Broad Spectrum Plant Secondary Metabolites Targeting the Spike Proteins of Omicron Variant and Wild-Type SARS-CoV-2

“…The 3D structures of the ligands {LOCM and those of the reference standard (zafirlukast [ 16 ], cefoperazone [ 17 ]), were obtained from PubChem “ (accessed on 15 January 2022)” and subsequently optimized via the addition of Gasteiger charges on UCSF chimera software V1.14 [ 18 ] in preparation for docking. Zafirlukast cefoperazone are good, repurposed drug candidates for COVID-19 targeting SARS-CoV-2 SP [ 16 , 17 ] and hence their selection as the reference standards in this study.…”

Efficient rescue of a newly classified Ebinur lake orthobunyavirus with GFP reporter and its application in rapid antiviral screening

“…But in our study, the favipiravir is ineffective even at higher concentrations, the specific reasons need to be further explored. As for the antiviral candidates we found in this research, diosmin and cyanidin-3-O-glucoside were identified as inhibitor of SARS-CoV-2, since diosmin could bind covalently to the SARS-CoV-2 main protease, inhibiting the infection pathway of SARS-CoV-2 (44), and cyanidin-3-O-glucoside was demonstrated to inhibit M protein activity of SARS-CoV-2 in a dose-dependent manner at biologically relevant (μM) concentrations (45). The other three compounds, clinodiside A, secoxyloganin and disogluside, have not been reported to have antiviral effects yet.…”