An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19.

An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19.

Science (New York, N.Y.) (2021-11-03)

Dafydd R Owen, Charlotte M N Allerton, Annaliesa S Anderson, Lisa Aschenbrenner, Melissa Avery, Simon Berritt, Britton Boras, Rhonda D Cardin, Anthony Carlo, Karen J Coffman, Alyssa Dantonio, Li Di, Heather Eng, RoseAnn Ferre, Ketan S Gajiwala, Scott A Gibson, Samantha E Greasley, Brett L Hurst, Eugene P Kadar, Amit S Kalgutkar, Jack C Lee, Jisun Lee, Wei Liu, Stephen W Mason, Stephen Noell, Jonathan J Novak, R Scott Obach, Kevin Ogilvie, Nandini C Patel, Martin Pettersson, Devendra K Rai, Matthew R Reese, Matthew F Sammons, Jean G Sathish, Ravi Shankar P Singh, Claire M Steppan, Al E Stewart, Jamison B Tuttle, Lawrence Updyke, Patrick R Verhoest, Liuqing Wei, Qingyi Yang, Yuao Zhu

PMID34726479

摘要

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.