PF-07304814, a phosphate prodrug of PF-00835231, acts as a potent 3CLpro protease (Mpro) inhibitor with SARS-CoV-2 antiviral activity. PF-07304814 binds and inhibits SARS-CoV-2 3CLpro activity with a Ki of 174nM. PF-07304814 is promising single antiviral agent and also can be used for the research of combination with other antivirals that target other critical stages of the coronavirus life cycle[1].
Once administered through intravenous infusion, PF-07304814 is cleaved into PF-00835231 to exert its anti-viral effects. PF-07304814 exhibits a favorable cardiovascular safety profile[1].PF-07304814 is administered intravenously to rats, dogs and monkeys. It exhibits high systemic clearance and short half-life across species forming 68, 81, 76% PF-00835231 in rats, dogs and monkey respectively in comparison to the systemic exposure achieved with IV administration of PF00835231[1].
[1]. Koen Vandyck, et al. Considerations for the discovery and development of 3-chymotrypsin-like cysteine protease inhibitors targeting SARS-CoV-2 infection. Curr Opin Virol. 2021 Apr 27;49:36-40.
[2]. Britton Boras, et al. Title: Discovery of a Novel Inhibitor of Coronavirus 3CL Protease as a Clinical Candidate for the Potential Treatment of COVID-19 Short Title: Novel 3CL Protease Inhibitor for COVID-19