Identification of potential natural inhibitors of SARS-CoV2 main protease by molecular docking and simulation studies

showed minimum binding score (-9.08 and -8.07 kcal/mole) against Mpro protein in comparison to shikonin and lopinavir (≈ -5.4 kcal/mole) a standard Mpro inhibitor. Furthermore, principal component analysis, free energy landscape and protein-ligand energy calculation studies revealed that these two compounds strongly bind to the catalytic core of the Mpro protein with higher efficacy than lopinavir, a standard antiretroviral of the protease inhibitor class. Taken together, this structure based optimization has provided lead on two natural Mpro inhibitors for further testing and development as therapeutics against human coronavirus.Communicated by Ramaswamy H. Sarma.