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

Keywords:

• 2019-nCOV
• COVID-19
• Remdesivir
• sequence analysis
• phylogeny
• molecular docking
• dynamics simulations

Acknowledgements

The authors are highly thankful to the Indian Council of Medical Research (DHR, MoHFW), New Delhi, Government of India, for providing facilities, and resources. MM and NP are highly thankful to TATA trust for providing facilities at the NIN-TATA Centre of Excellence in Public Health and Nutrition, ICMR-National Institute of Nutrition, Hyderabad, Telangana State.

Author contributions statement

Manne Munikumar, Vankudavath Raju Naik and Ungarala Ramakrishna conceived and developed the methods and carried out the analysis of the sequence analysis, molecular docking and dynamics simulations under the supervision of Boiroju Naveen Kumar and Rajkumar Hemalatha. Medithi Srujana, Giridhar Goudar and Naresh Pittla performed literature review, interpreted results, drafted the initial manuscript, and revised the co-authors inputs and additions. All authors revised and reviewed the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).