Studies on Computational Molecular Interaction Between SARS-CoV-2 Main Protease and Natural Products

A combination of docking approaches, scoring functions, molecular dynamic simulation, and literature mining have been employed to screen readily available natural products (unique 27256 chemical entities, 598435 unique compounds), which can inhibit the SARS-CoV-2 main protease. Theaflavin digallate, a major constituent of black tea, has been observed to be as three top hits after the virtual screening of 598435 unique compounds. The main protease-theaflavin digallate complex appeared to be in the metastable stage and interact with critical active site residues of the main protease during molecular dynamics simulation for 200 ns. Invitro evidence on main protease inhibition of 2003 SARS-CoV by theaflavin digallate is available in the scientific literature. As evident by the dynamics of intermolecular interactions, theaflavin digallate, forms approximately three hydrogen bonds with Glu166 of main protease, mostly through hydroxyl groups in the benzene ring of benzo(7) annulen-6-one. Glu166 is the most critical amino acid for main protease dimerization, which in turn, is necessary for catalytic activity. We have employed chloroquine and epigallocatechin gallate (green tea component) as a control set. Based on computational molecular interaction and data available in scientific literature, theaflavin digallate can inhibit the main protease of SARS-CoV-2.