Computational basis of SARS-CoV 2 main protease inhibition: an insight from molecular dynamics simulation based findings.
J Biomol Struct Dyn
; : 1-11, 2021 May 13.
Article
in English
| MEDLINE | ID: covidwho-2250606
ABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic is caused by newly discovered severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). One of the striking targets amongst all the proteins in coronavirus is the main protease (Mpro), as it plays vital biological roles in replication and maturation of the virus, and hence the potential target. The aim of this study is to repurpose the Food and Drug Administration (FDA) approved molecules via computer-aided drug designing against Mpro (PDB ID 6Y2F) of SARS CoV-2 due to its high x-ray resolution of 1.95 Å as compared to other published Mprostructures. High Through Virtual Screening (HTVS) of 2456 FDA approved drugs using structure-based docking were analyzed. Molecular Dynamics simulations were performed to check the overall structural stability (RMSD), Cα fluctuations (RMSF) and protein-ligand interactions. Further, trajectory analysis was performed to assess the binding quality by exploiting the protein-residue motion cross correlation (DCCM) and binding free energy (MM/GBSA). Tenofovir, an antiretroviral for HIV-proteases and Terlipressin, a vasoconstrictor show stable RMSD, RMSF, better MM/GBSA with good cross correlation as compared to the Apo and O6K. Moreover, the results show concurrence with Nelfinavir, Lopinavir and Ritonavir which have shown significant inhibition in in vitro studies. Therefore, we conclude that Tenofovir and Terlipresssin might also show protease inhibition but are still open to clinical validation in case of SARS-CoV 2 treatment.Communicated by Ramaswamy H. Sarma.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Type of study:
Prognostic study
/
Randomized controlled trials
Language:
English
Journal:
J Biomol Struct Dyn
Year:
2021
Document Type:
Article
Affiliation country:
07391102.2021.1922310
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