A Drug Repurposing Approach to Identify Therapeutics by Screening Pathogen Box Exploiting SARS-CoV-2 Main Protease.
Chem Biodivers
; 20(2): e202200600, 2023 Feb.
Article
in English
| MEDLINE | ID: covidwho-2172732
ABSTRACT
Coronavirus disease-19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2) and is responsible for a higher degree of morbidity and mortality worldwide. There is a smaller number of approved therapeutics available to target the SARS-CoV-2 virus, and the virus is evolving at a fast pace. So, there is a continuous need for new therapeutics to combat COVID-19. The main protease (Mpro ) enzyme of SARS-CoV-2 is essential for replication and transcription of the viral genome, thus could be a potent target for the treatment of COVID-19. In the present study, we performed an in-silico screening analysis of 400 diverse bioactive inhibitors with proven antibacterial and antiviral properties against Mpro drug target. Ten compounds showed a higher binding affinity for Mpro than the reference compound (N3), with desired physicochemical properties. Furthermore, in-depth docking and superimposition revealed that three compounds (MMV1782211, MMV1782220, and MMV1578574) are actively interacting with the catalytic domain of Mpro . In addition, the molecular dynamics simulation study showed a solid and stable interaction of MMV178221-Mpro complex compared to the other two molecules (MMV1782220, and MMV1578574). In line with this observation, MM/PBSA free energy calculation also demonstrated the highest binding free energy of -115.8â
kJ/mol for MMV178221-Mpro compound. In conclusion, the present in silico analysis revealed MMV1782211 as a possible and potent molecule to target the Mpro and must be explored inâ
vitro and inâ
vivo to combat the COVID-19.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
COVID-19
Type of study:
Observational study
/
Prognostic study
Limits:
Humans
Language:
English
Journal:
Chem Biodivers
Journal subject:
Biochemistry
/
Chemistry
Year:
2023
Document Type:
Article
Affiliation country:
Cbdv.202200600
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