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

Naik, Vankudavath Raju; Munikumar, Manne; Ramakrishna, Ungarala; Srujana, Medithi; Goudar, Giridhar; Naresh, Pittla; Kumar, Boiroju Naveen; Hemalatha, Rajkumar

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, in silico 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 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 ns simulations run and found stable (∼99%) by RMSD and RMSF. Thus, present in silico study at molecular approaches suggest that, Remdesivir is a potent therapeutic inhibitor against 2019-nCoV. Communicated by Ramaswamy H. Sarma