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

Abstract

<div> <div> <div> <p>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. </p> </div> </div> </div>

Combinedin silicodocking and in vitro antiviral testing for drug repurposing identified lurasidone and elbasvir as SARS-CoV-2 and HCoV-OC43 inhibitors

“…Grazoprevir inhibited SARS-CoV-2 with an EC50 around 16 µM (CC50 value >100 µM). Published computational studies suggested grazoprevir as a potential inhibitor of the nucleocapsid protein or the papain-like protease of SARS-CoV-2 (Behera et al, 2020).…”