Remdesivir (GS-5734) as a therapeutic option of 2019-nCOV main protease – <i>in silico</i> approach

Abstract

2019 - Novel Coronavirus (2019-nCOV), enclosed large genome positive-sense RNA virus characterized by crown-like spikes that protrude from their surface, and have a distinctive replication strategy. The 2019-nCOV belongs to the Coronaviridae family, principally consists of virulent pathogens showing zoonotic property, has emerged as a pandemic outbreak with high mortality and high morbidity rate around the globe and no therapeutic vaccine or drugs against 2019-nCoV are discovered till now. In this study, <i>in silico</i> methods and algorithms were used for sequence, structure analysis and molecular docking on M^pro of 2019-nCOV. The co-crystal structure of 2019-nCOV protease, 6LU7 have ∼99% identity with SARS-CoV protease. The 6LU7 residues, Cys145 and His164 are playing a significant role in replication and are essential for the survival of 2019-nCOV. Alongside, 2019-nCOV M^pro sequence is non-homologous to human host-pathogen. Complete genome sequence analysis, structural and molecular docking results revealed that Remdesivir is having a better binding affinity with -8.2<b> </b>kcal/mol than the rest of protease inhibitors, and peptide. Remdesivir is strongly forming h-bonds with crucial M^pro residues, Cys145, and His164. Further, MD simulation analysis also confirmed, that these residues are forming H-bond with Remdesivir during 100<b> </b>ns simulations run and found stable (∼99%) by RMSD and RMSF. Thus, present <i>in silico</i> study at molecular approaches suggest that, Remdesivir is a potent therapeutic inhibitor against 2019-nCoV.Communicated by Ramaswamy H. Sarma.