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Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID-19

Medicine and Health

Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID-19

B. Boras, R. M. Jones, et al.

Discover how PF-07304814, a groundbreaking phosphor prodrug of the potent 3CL protease inhibitor PF-00835231, could revolutionize COVID-19 treatment. With impressive antiviral effects and promising synergy with remdesivir, this innovative research, conducted by a team including Britton Boras and Dan Arenson, paves the way for new therapeutic options against coronaviruses.

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Playback language: English
Abstract
COVID-19, caused by SARS-CoV-2, is a global pandemic. 3CL protease, essential for coronavirus replication, lacks close human analogs. PF-00835231, a 3CL protease inhibitor, shows potent in vitro antiviral activity. This paper details PF-07304814, a phosphate prodrug of PF-00835231, designed for improved delivery and sustained systemic exposure. PF-00835231 exhibits broad-spectrum activity against coronaviruses and additive/synergistic effects with remdesivir. ADME, safety, in vitro, and in vivo data support clinical evaluation of PF-07304814 as a potential COVID-19 treatment.
Publisher
Nature Communications
Published On
Oct 18, 2021
Authors
Britton Boras, Rhys M. Jones, Brandon J. Anson, Dan Arenson, Lisa Aschenbrenner, Malina A. Bakowski, Nathan Beutler, Joseph Binder, Emily Chen, Heather Eng, Holly Hammond, Jennifer Hammond, Robert E. Haupt, Robert Hoffman, Eugene P. Kadar, Rob Kania, Emi Kimoto, Melanie G. Kirkpatrick, Lorraine Lanyon, Emma K. Lendy, Jonathan R. Lillis, James Logue, Suman A. Luthra, Chunlong Ma, Stephen W. Mason, Marisa E. McGrath, Dafydd Owen, R. Scott Obach, Matthew N. O'Brien, Rebecca O'Connor, Kevin Ogilvie, Martin Pettersson, Matthew R. Reese, Thomas F. Rogers, Romel Rosales, Michelle I. Rossulek, Jean G. Sathish, Norimitsu Shirai, Claire Steppan, Martyn Ticehurst, Lawrence W. Updyke, Stuart Weston, Yuao Zhu, Kris M. White, Adolfo García-Sastre, Jun Wang, Arnab K. Chatterjee, Andrew D. Mesecar, Matthew B. Frieman, Annaliesa S. Anderson, Charlotte Allerton
Tags
COVID-19
SARS-CoV-2
3CL protease inhibitor
PF-07304814
antiviral activity
clinical evaluation
therapeutic options

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