Computational drug repurposing study elucidating simultaneous inhibition of entry and replication of novel corona virus by Grazoprevir.
Sci Rep
; 11(1): 7307, 2021 03 31.
Article
in English
| MEDLINE | ID: covidwho-1164913
ABSTRACT
Outcomes of various clinical studies for the coronavirus disease 2019 (COVID-19) treatment indicated that the drug acts via inhibition of multiple pathways (targets) is likely to be more successful and promising. Keeping this hypothesis intact, the present study describes for the first-time, Grazoprevir, an FDA approved anti-viral drug primarily approved for Hepatitis C Virus (HCV), mediated multiple pathway control via synergistic inhibition of viral entry targeting host cell Angiotensin-Converting Enzyme 2 (ACE-2)/transmembrane serine protease 2 (TMPRSS2) and viral replication targeting RNA-dependent RNA polymerase (RdRP). Molecular modeling followed by in-depth structural analysis clearly demonstrated that Grazoprevir interacts with the key residues of these targets. Futher, Molecular Dynamics (MD) simulations showed stability and burial of key residues after the complex formation. Finally, Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) analysis identified the governing force of drug-receptor interactions and stability. Thus, we believe that Grazoprevir could be an effective therapeutics for the treatment of the COVID-19 pandemic with a promise of unlikely drug resistance owing to multiple inhibitions of eukaryotic and viral proteins, thus warrants further clinical studies.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Quinoxalines
/
Sulfonamides
/
Carbamates
/
Cyclopropanes
/
Amides
/
Angiotensin-Converting Enzyme 2
/
Coronavirus RNA-Dependent RNA Polymerase
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
Sci Rep
Year:
2021
Document Type:
Article
Affiliation country:
S41598-021-86712-2
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