Discovery of a Novel Inhibitor of Coronavirus 3CL Protease as a Clinical Candidate for the Potential Treatment of COVID-19.

BioRxiv : the Preprint Server for Biology
Britton BorasCharlotte Allerton

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 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-00835231 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.

Citations

Jan 14, 2021·The Biochemical Journal·George M Burslem
Mar 27, 2021·Proceedings of the National Academy of Sciences of the United States of America·Xi HeDai Wang
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mohammad Hassan BaigJae-June Dong
Apr 24, 2021·Journal of Medicinal Chemistry·Naoya KitamuraJun Wang
Jun 11, 2021·Computational and Structural Biotechnology Journal·Peerapon DeetanyaKittikhun Wangkanont
Jan 9, 2021·ACS Infectious Diseases·Mark N Namchuk
Feb 12, 2021·ACS Infectious Diseases·Kas SteutenMatthew Bogyo

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Methods Mentioned

BETA
thermal-shift
X-ray
thermal shift
equilibrium dialysis

Clinical Trials Mentioned

NCT04627532
NCT04535167

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