Screening of Severe Acute Respiratory Syndrome Coronavirus 2 RNA-Dependent RNA Polymerase Inhibitors Using Computational Approach.
J Comput Biol
; 28(12): 1228-1247, 2021 12.
Article
in English
| MEDLINE | ID: covidwho-1545879
ABSTRACT
The detrimental effect of coronavirus disease 2019 (COVID-19) pandemic has manifested itself as a global crisis. Currently, no specific treatment options are available for COVID-19, so therapeutic interventions to tackle the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection must be urgently established. Therefore, cohesive and multidimensional efforts are required to identify new therapies or investigate the efficacy of small molecules and existing drugs against SARS-CoV-2. Since the RNA-dependent RNA Polymerase (RdRP) of SARS-CoV-2 is a promising therapeutic target, this study addresses the identification of antiviral molecules that can specifically target SARS-CoV-2 RdRP. The computational approach of drug development was used to screen the antiviral molecules from two antiviral libraries (Life Chemicals [LC] and ASINEX) against RdRP. Here, we report six antiviral molecules (F3407-4105, F6523-2250, F6559-0746 from LC and BDG 33693278, BDG 33693315, LAS 34156196 from ASINEX), which show substantial interactions with key amino acid residues of the active site of SARS-CoV-2 RdRP and exhibit higher binding affinity (>7.5 kcalmol-1) than Galidesivir, an Food and Drug Administration-approved inhibitor of the same. Further, molecular dynamics simulation and Molecular Mechanics Poisson-Boltzmann Surface Area results confirmed that identified molecules with RdRP formed higher stable RdRP-inhibitor(s) complex than RdRP-Galidesvir complex. Our findings suggest that these molecules could be potential inhibitors of SARS-CoV-2 RdRP. However, further in vitro and preclinical experiments would be required to validate these potential inhibitors of SARS-CoV-2 protein.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Drug Evaluation, Preclinical
/
Drug Discovery
/
Pandemics
/
Computational Chemistry
/
Coronavirus RNA-Dependent RNA Polymerase
/
SARS-CoV-2
/
COVID-19 Drug Treatment
Type of study:
Prognostic study
Topics:
Traditional medicine
Language:
English
Journal:
J Comput Biol
Journal subject:
Molecular Biology
/
Medical Informatics
Year:
2021
Document Type:
Article
Affiliation country:
Cmb.2020.0639
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