tetano
Editor, Senior Moderator
J Biomol Struct Dyn
. 2020 Jun 22;1-14.
doi: 10.1080/07391102.2020.1781694. Online ahead of print.
Remdesivir (GS-5734) as a Therapeutic Option of 2019-nCOV Main Protease - in silico Approach
Vankudavath Raju Naik[SUP] 1 [/SUP], Manne Munikumar[SUP] 2 [/SUP], Ungarala Ramakrishna[SUP] 3 [/SUP], Medithi Srujana[SUP] 4 [/SUP], Giridhar Goudar[SUP] 5 [/SUP], Pittla Naresh[SUP] 2 [/SUP], Boiroju Naveen Kumar[SUP] 6 [/SUP], Rajkumar Hemalatha[SUP] 7 [/SUP]
Affiliations
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[SUP]pro[/SUP] 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[SUP]pro[/SUP] 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 -8.2kcal/mol than the rest of protease inhibitors, and peptide. Remdesivir is strongly forming h-bonds with crucial M[SUP]pro[/SUP] residues, Cys145, and His164. Further, MD simulation analysis also confirmed, that these residues are forming H-bond with Remdesivir during 100ns 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; dynamics simulations; molecular docking; phylogeny; sequence analysis.
. 2020 Jun 22;1-14.
doi: 10.1080/07391102.2020.1781694. Online ahead of print.
Remdesivir (GS-5734) as a Therapeutic Option of 2019-nCOV Main Protease - in silico Approach
Vankudavath Raju Naik[SUP] 1 [/SUP], Manne Munikumar[SUP] 2 [/SUP], Ungarala Ramakrishna[SUP] 3 [/SUP], Medithi Srujana[SUP] 4 [/SUP], Giridhar Goudar[SUP] 5 [/SUP], Pittla Naresh[SUP] 2 [/SUP], Boiroju Naveen Kumar[SUP] 6 [/SUP], Rajkumar Hemalatha[SUP] 7 [/SUP]
Affiliations
- PMID: 32568620
- DOI: 10.1080/07391102.2020.1781694
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[SUP]pro[/SUP] 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[SUP]pro[/SUP] 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 -8.2kcal/mol than the rest of protease inhibitors, and peptide. Remdesivir is strongly forming h-bonds with crucial M[SUP]pro[/SUP] residues, Cys145, and His164. Further, MD simulation analysis also confirmed, that these residues are forming H-bond with Remdesivir during 100ns 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; dynamics simulations; molecular docking; phylogeny; sequence analysis.