Discovery of a Novel Inhibitor of Coronavirus 3CL Protease as a Clinical Candidate for the Potential Treatment of COVID-19
Rhys M. Jones,
Brandon J. Anson,
Malina A. Bakowski,
Eugene P. Kadar,
Melanie G. Kirkpatrick,
Emma K. Lendy,
Jonathan R. Lillis,
Suman A. Luthra,
R. Scott Obach,
Matthew N. O’ Brien,
Matthew R Reese,
Thomas F Rogers,
Michelle I. Rossulek,
Jean G. Sathish,
Lawrence W. Updyke,
Arnab K. Chatterjee,
Andrew D. Mesecar,
Annaliesa S. Anderson,
Posted 13 Sep 2020
bioRxiv DOI: 10.1101/2020.09.12.293498
Posted 13 Sep 2020
COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is a virally encoded protein that is essential to the viral life cycle across a broad spectrum of coronaviruses with no close human analogs. The designed phosphate prodrug PF-07304814 is metabolized to PF-00835321 which is a potent inhibitor in vitro of the coronavirus family 3CL pro, with selectivity over human host protease targets. Furthermore, PF-00835231 exhibits potent in vitro antiviral activity against SARS-CoV-2 as a single agent and it is additive/synergistic in combination with remdesivir. We present the ADME, safety, and in vitro antiviral activity data to warrant clinical evaluation. One Sentence Summary The phosphate prodrug PF-07304814 is disclosed as an investigational novel intravenous small molecule 3CL protease inhibitor for COVID-19. ### Competing Interest Statement A.D.M has a sponsored program contract with Pfizer to test compounds for inhibition of coronavirus proteases. JW has a sponsored research agreement with Pfizer to test compounds for inhibition of coronavirus proteases.
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