Binary-QSAR guided virtual screening of FDA approved drugs and compounds in\rclinical investigation against SARS-CoV-2 main protease

Abstract

: With the emergence of the new SARS-CoV-2 virus, drug repurposing studies have gained substantial importance. Combined\rwith the efficacy of recent improvements in ligand- and target-based virtual screening approaches, virtual screening has become faster\rand more productive than ever. In the current study, an FDA library of approved drugs and compounds under clinical investigation were\rscreened for their antiviral activity using the antiviral therapeutic activity binary QSAR model of the MetaCore/MetaDrug platform.\rAmong 6733-compound collection, we found 370 compounds with a normalized therapeutic activity value greater than a cutoff of 0.75.\rOnly these selected compounds were used for molecular docking studies against the SARS-CoV-2 main protease $(M^{pro}).$ After initial\rshort (10 ns) molecular dynamics (MD) simulations with the top-50 docking scored compounds and following molecular mechanics\rgeneralized born surface area (MM/GBSA) calculations, top-10 compounds were subjected to longer (100 ns) MD simulations and\rend-point MM/GBSA estimations. Our virtual screening protocol yielded Cefuroxime pivoxetil, an ester prodrug of second-generation\rcephalosporin antibiotic Cefuroxime, as being a considerable molecule for drug repurposing against the $SARS-CoV-2 M^{pro}.$