Abstract
COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is a virally encoded protein that is essential 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, in vitro, and in vivo antiviral activity data that supports the clinical evaluation of this compound as a potential COVID-19 treatment.
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. The Frieman Laboratory was funded by Pfizer for the work in this manuscript.
Footnotes
One Sentence Summary: PF-07304814, a novel phosphate prodrug is disclosed as an investigational novel intravenous small molecule 3CL protease inhibitor for the potential treatment of COVID-19 and other coronavirus infections.
One small typo in the abstract. The compound ID number should be PF-00835231 and in the abstract the number is PF-00835321 in one place. This has been corrected in the abstract and in the manuscript. Version 3: Added in vivo efficacy data, section Activity of PF-00835231 in a mouse model of SARS-CoV-1 infection and Figure 4.
