COVID-19: docking-based virtual screening and molecular dynamics study to identify potential SARS-CoV-2 spike protein...

A novel coronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enters into the host cells through an interaction between its surface spike protein (S-protein) and the angiotensin-converting enzyme 2 receptors, leading to coronavirus disease 2019 (COVID-19). Using effective S-protein inhibitors may reduce the virulence of the virus. Molecular docking was performed to evaluate the binding affinity of 97 phenolic compounds (phenolics) with the SARS-CoV-2 S-protein receptor-binding domain (RBD). Molecular dynamics (MD) simulation was carried out to assess the stability of interactions between top-ranked compounds and S-protein RBD. Pharmacokinetics and toxicity of top-ranked inhibitors were also studied. Furthermore, the essential residues involved in ligand binding, based on the degree of each amino acid in the ligand-amino acid interaction (LAI) network for S-protein, were identified. Molecular docking and MD simulations were performed utilizing the AutoDock and Discovery Studio Client version, respectively. The LAI network was analyzed using the Cytoscape software. Pharmacokinetics and toxicity of top-ranked compounds were studied using bioinformatics webservers. It was estimated that nine of the studied phenolics can bind to the SARS-CoV-2 S-protein at the nanomolar scale with a considerable estimated energy of binding (∆G binding Keywords: COVID-19; drug; molecular docking; molecular dynamics; SARS-CoV-2; spike protein.