학술논문
An oral SARS-CoV-2 M (pro) inhibitor clinical candidate for the treatment of COVID-19
Document Type
Academic Journal
Author
Owen, Dafydd R.; Allerton, Charlotte M. N.; Anderson, Annaliesa S.; Aschenbrenner, Lisa; Avery, Melissa; Berritt, Simon; Boras, Britton; Cardin, Rhonda D.; Carlo, Anthony; Coffman, Karen J.; Dantonio, Alyssa; Di, Li; Eng, Heather; Ferre, Rose Ann; Gajiwala, Ketan S.; Gibson, Scott A.; Greasley, Samantha E.; Hurst, Brett L.; Kadar, Eugene P.; Kalgutkar, Amit S.; Lee, Jack C.; Lee, Jisun; Liu, Wei; Mason, Stephen W.; Noell, Stephen; Novak, Jonathan J.; Obach, R. Scott; Ogilvie, Kevin; Patel, Nandini C.; Pettersson, Martin; Rai, Devendra K.; Reese, Matthew R.; Sammons, Matthew F.; Sathish, Jean G.; Singh, Ravi Shankar P.; Steppan, Claire M.; Stewart, Al E.; Tuttle, Jamison B.; Updyke, Lawrence; Verhoest, Patrick R.; Wei, Liuqing; Yang, Qingyi; Zhu, Yuao
Source
Science. December 24, 2021, Vol. 374 Issue 6575, p1586, 8 p.
Subject
Language
English
ISSN
0036-8075
Abstract
The worldwide outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. Alongside vaccines, antiviral therapeutics are an important part of the healthcare response to countering the ongoing threat presented by COVID-19. Here, we report the discovery and characterization of PF-07321332, an orally bioavailable SARS-CoV-2 main protease inhibitor with in vitro pan-human coronavirus antiviral activity and excellent off-target selectivity and in vivo safety profiles. PF-07321332 has demonstrated oral activity in a mouse-adapted SARS-CoV-2 model and has achieved oral plasma concentrations exceeding the in vitro antiviral cell potency in a phase 1 clinical trial in healthy human participants.