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Simultaneous Inhibition of Entry and Replication of Novel Corona Virus by Grazoprevir: A Computational Drug Repurposing Study

preprint
submitted on 05.06.2020 and posted on 05.06.2020 by Santosh Kumar Behera, Nazmina Vhora, Darshan Contractor, Amit Shard, Dinesh Kumar, Kiran Kalia, Alok Jain

It is evident from the on-going clinical studies (trials) for coronavirus disease 2019 (COVID-19) that treatment with a single drug is not likely to be sufficient. This, in turn, suggests that the drug acts via inhibition of multiple pathways 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 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). We believe that Grazoprevir either alone or given in combination could be effective therapeutics for treatment of COVID-19 pandemic with a promise of unlikely drug resistance owing to multiple inhibition of eukaryotic and viral proteins.

Funding

Department of Pharmaceuticals (DoP), Ministry of Chemical and Fertilizers

DST-SERB (Ramanujan Fellowship: File No. SB/S2/RJN-135/2017)

DBT (Ramalingaswami Fellowship)

IIT-Delhi HPC facility for computational resources (Project No: C19-3)

History

Email Address of Submitting Author

alokjain16@gmail.com

Institution

National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A)

Country

India

ORCID For Submitting Author

0000-0002-7365-7455

Declaration of Conflict of Interest

No conflict of interest

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