Molecular insights into the <i>in silico</i> discovery of corilagin from <i>Terminalia chebula</i> as a potential dual inhibitor of SARS-CoV-2 structural proteins
Sushma Pradeep, Shashank M. Patil, Chandan Dharmashekara, Anisha Jain, Ramith Ramu, Prithvi S. Shirahatti, Subhankar P. Mandal, Pruthvish Reddy, Chandrashekar Srinivasa, Sharanagouda S. Patil, Joaquín Ortega‐Castro, Juan Frau, Norma Flores‐Holguín, Chandan Shivamallu, Shiva Prasad Kollur, Daniel Glossman‐Mitnik
Abstract
were subjected to a series of computational investigations including molecular docking simulations, molecular dynamics (MD) simulations, binding free energy calculations, and PASS pharmacological analysis. The results obtained from these studies revealed that corilagin was highly interactive with the S (-8.9 kcal/mol) and N (-9.2 kcal/mol) proteins, thereby showing dual inhibition activity. It was also found to be stable enough to induce biological activity inside the inhibitor binding pocket of the target enzymes throughout the dynamics simulation run for 100 ns. This is also confirmed by the changes in the protein conformations, evaluated using free energy landscapes. Outcomes from this investigation identify corilagin as the lead potential dual inhibitor of S and N proteins of SARS-CoV-2, which could be taken for biological studies in near future.Communicated by Ramaswamy H. Sarma.