With the emergence of the new SARS-CoV-2 virus, drug repurposing studies have gained substantial importance. Combined with the efficacy of recent improvements in ligand- and target-based virtual screening approaches, virtual screening has become faster and more productive than ever. In the current study, an FDA library of approved drugs and compounds under clinical investigation were screened for their antiviral activity using the antiviral therapeutic activity binary QSAR model of the MetaCore/MetaDrug platform. Among 6733-compound collection, we found 370 compounds with a normalized therapeutic activity value greater than a cutoff of 0.75. Only these selected compounds were used for molecular docking studies against the SARS-CoV-2 main protease (M pro ). After initial short (10 ns) molecular dynamics (MD) simulations with the top-50 docking scored compounds and following molecular mechanics generalized born surface area (MM/GBSA) calculations, top-10 compounds were subjected to longer (100 ns) MD simulations and end-point MM/GBSA estimations. Our virtual screening protocol yielded Cefuroxime pivoxetil, an ester prodrug of second-generation cephalosporin antibiotic Cefuroxime, as being a considerable molecule for drug repurposing against the SARS-CoV-2 M pro .
【저자키워드】 Drug repurposing, SARS-CoV-2, Virtual screening, Binary QSAR, 【초록키워드】 Efficacy, protocol, Antiviral, docking, protease, antiviral activity, FDA, virus, MD simulation, cefuroxime, improvement, molecular, platform, antibiotic, Ligand, approved drug, approaches, Molecular docking study, Compound, M pro, Cutoff, clinical investigation, therapeutic activity, new SARS-CoV-2, Combined, initial, greater, selected, screened, were used, faster, normalized, scored, the SARS-CoV-2, 【제목키워드】 SARS-CoV-2 main protease, FDA approved drug, Compound, clinical investigation,