In silico prediction of interactions and molecular dynamics simulation analysis of Mpro of Severe Acute Respiratory Syndrome caused by novel coronavirus 2 with the FDA-approved nonprotein antiviral drugs
Subramaniam Sivakumar, Sugumar Mohanasundaram, Narasimhan Rangarajan, V. Sampath, M.V. Dass Prakash
Abstract
In the current scenario of the severe acute respiratory syndrome caused by novel coronavirus 2 (SARS-CoV-2) pandemic, the repurposing of the Food and Drug Administration (FDA)-approved antiviral drugs for the possibility of treating SARS-CoV-2 is an unavoidable scientific method. It further exemplifies the physical interactions between the target protein and the chosen drugs. In this study, the main protease (M pro ) structure of SARS-CoV-2 Protein Data Bank ID: 7BUY with 42 FDA-approved antiviral drugs was analyzed by molecular docking using PyRx-Vina, and the amino acids involved in docking are analyzed using Discovery Studio Visualizer. The protein-drug complex stability was analyzed by molecular dynamics simulation (MDS) using GROMACS. The results showed that ledipasvir showed the maximum binding affinity (-10.4 kcal/mol) with M pro of SARS-CoV-2 followed by paritaprevir (-9.1 kcal/mol) and velpatasvir (-8.8 kcal/mol). These three compounds are found to have a significant number of interactions. Moreover, ledipasvir and velpatasvir showed similar interactions at GLU240, PRO241, ILE249, PRO293, and VAL202. MDS showed that the top ligands had formed stable complexes with M pro . Molecular Mechanics Poisson-Boltzmann Surface Area calculation revealed thermodynamically stable binding energies of -195.370 1.119 kJ/mol and -180.778 0.868 kJ/mol for ledipasvir and velpatasvir, respectively. Paritaprevir showed stable binding energy of -75.679 0.922 kJ/mol with M pro of SARS-CoV-2.