Unraveling bioactive metabolites of mangroves as putative inhibitors of SARS-CoV-2 Mpro and RBD proteins: molecular dynamics and ADMET analysis

COVID-19 is a deadly pandemic caused by Corona virus leading to millions of deaths worldwide. Till today no medicine was available to cure this disease. This study selected 262 potential bioactive natural products derived from mangroves to inhibit the main protease (Mpro) and receptor-binding domain (RBD) protein of the COVID-19 virus. All the ligands were subjected to Adsorption Digestion Metabolism Excretion and Toxicity (ADMET) predictions and docking studies using AutodockVina. Among all the ligands, NP_143 (Shearinine A) and NP_242 (Amentoflavone), having the highest docking score of 10.2 and 10.1 Kj/mole, respectively, were picked for 100 ns of Molecular Dynamics using GROMACS. The trajectories generated were used to estimate Root mean square deviation (RMSD), Root mean square fluctuations (RMSF), Radius of Gyrations (RG), Solvent accessible surface area (SASA), and Hydrogen bonds. From the data generated, both the ligands have good binding ability at the active site of Mpro protein and do not deviate much. They have strong interactions with the amino acids during the 100 ns of simulations and can thus be considered potential drug candidates. Communicated by Ramaswamy H. Sarma SARS-CoV-2 Mpro plays a pivotal role in viral replication and serves as important drug target. Bioactive compounds of mangroves origin are promising source of antiviral drugs. ADMET and docking study explored two lead compounds from mangroves against Mpro. MD simulation validated ligands of lead compounds had stronger binding affinity with Mpro.