Molecular Docking Simulation Studies, Toxicity Study, Bioactivity Prediction, and Structure-Activity Relationship Reveals Rutin as a Potential Inhibitor of SARS-CoV-2 3CL pro
James H. Zothantluanga
Abstract
Coronavirus disease 2019 (COVID-19) pandemic has infected billions and has killed millions of people.Despite the advancement in drugs and vaccines, the COVID-19 pandemic rages on.Bioactive compounds of medicinal plants with antiviral properties such as flavonoids might be useful as phytotherapy for COVID-19.The present study aims to evaluate 16 flavonoids and identify a potential inhibitor for the main protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 3CL pro) which is responsible for replication of the viral genome in a host cell.Among the 16 flavonoids, molecular docking simulation studies reveal that rutin has the highest binding affinity towards chain A, chain B, chain C, and chain D of SARS-CoV-2 3CL pro.Rutin formed conventional hydrogen bonds and non-covalent hydrophobic bonds with important amino acid residues at the active binding site of SARS-CoV-2 3CL pro.Also, rutin was computed to be non-toxic.Rutin had a better drug-likeness score and protease inhibition than the co-crystal inhibitor of SARS-CoV-2 3CL pro.The structure-activity relationship revealed important moieties of rutin that might be essential for the inhibition of SARS-CoV-2 3CL pro.The in-silico evidence suggests rutin may inhibit SARS-CoV-2 3CL pro and advocates its use as a phytotherapy for COVID-19.