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

Santosh Kumar Behera, Nazmina Vhora, Darshan Contractor, Amit Shard, Dinesh Kumar, Kiran Kalia, Alok Jain

10.26434/chemrxiv.12434174.v1

Research curated

Abstract

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.

Source: ChemRxiv

Related molecules

Name	Synonyms	Genes
RNA dependent RNA polymerase	RDR, viral RNA polymerase, RdRp, nsp12	rep, ORF1a-1b, RdRp
Transmembrane serine 2	TMPRSS2, Serine protease 10	TMPRSS2, PRSS10
Angiotensin-converting enzyme 2	ACE-related carboxypeptidase, ACE2	ACE2
Grazoprevir	Grazoprevir,1350514-68-9,MK5172,UNII-8YE81R1X1J, MK 5172

Related interactions

Target	Drug	Type	Result
RNA dependent RNA polymerase	Grazoprevir	Computational	positive
Angiotensin-converting enzyme 2	Grazoprevir	Computational	positive
Transmembrane serine 2	Grazoprevir	Computational	positive