Screening of potent phytochemical inhibitors against SARS-CoV-2 protease and its two Asian mutants

COVID-19, declared a pandemic in March 2020 by the World Health Organization is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The virus has already killed more than 2.3 million people worldwide. The principal intent of this work was to investigate lead compounds by screening natural product library (NPASS) for possible treatment of COVID-19. Pharmacophore features were used to screen a large database to get a small dataset for structure-based virtual screening of natural product compounds. In the structure-based screening, molecular docking was performed to find a potent inhibitor molecule against the main protease (Mpro) of SARS-CoV-2 (PDB ID: 6Y7M). The predicted lead compound was further subjected to Molecular Dynamics (MD) simulation to check the stability of the leads compound with the evolution of time. In pharmacophore-based virtual screening, 2,361 compounds were retained out of 30,927. In the structure-based screening, the lead compounds were filtered based on their docking scores. Among the 2,360 compounds, 12 lead compounds were selected based on their docking score. Kazinol T with NPASS ID: NPC474104 showed the highest docking score of −14.355 and passed criteria of Lipinski's drug-like parameters. Monitoring ADMET properties, Kazinol T showed its safety for consumption. Docking of Kazinol T with two Asian mutants (R60C and I152V) showed variations in binding and energy parameters. Normal mode analysis for ligand-bound and unbound form of protease along with its mutants, revealed displacement and correlation parameters for C-alpha atoms. MD simulation results showed that all ligand-protein complexes remained intact and stable in a dynamic environment with negative Gibbs free energy. The natural product Kazinol T was a predicted lead compound against the main protease of SARS-CoV-2 and will be the possible treatment for COVID-19. •A library of natural products was screened against the wild-type main protease and its two Asian mutants of SARS-CoV-2.•The Natural Product Activity and Species Source database (NPASS) database contain 30,927 compounds.•Pharmacophore and structure-based approaches were used for virtual screening.•The top-ranked compound was selected to evaluate its ADMET properties.•Molecular Dynamics simulation was performed to check the interaction and stability of the protein-ligand complex.•Kazinol T (NPASS ID: NPC474104) showed the highest docking score (−14.355 kcal/mol).