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. 2021 Dec 24;374(6575):1586-1593.
doi: 10.1126/science.abl4784. Epub 2021 Nov 2.

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

Dafydd R Owen  1 , Charlotte M N Allerton  1 , Annaliesa S Anderson  2 , Lisa Aschenbrenner  3 , Melissa Avery  3 , Simon Berritt  3 , Britton Boras  4 , Rhonda D Cardin  2 , Anthony Carlo  3 , Karen J Coffman  3 , Alyssa Dantonio  3 , Li Di  3 , Heather Eng  3 , RoseAnn Ferre  4 , Ketan S Gajiwala  4 , Scott A Gibson  5 , Samantha E Greasley  4 , Brett L Hurst  5 , Eugene P Kadar  3 , Amit S Kalgutkar  1 , Jack C Lee  3 , Jisun Lee  3 , Wei Liu  4 , Stephen W Mason  2 , Stephen Noell  3 , Jonathan J Novak  3 , R Scott Obach  3 , Kevin Ogilvie  3 , Nandini C Patel  1 , Martin Pettersson  1 , Devendra K Rai  2 , Matthew R Reese  3 , Matthew F Sammons  1 , Jean G Sathish  2 , Ravi Shankar P Singh  1 , Claire M Steppan  3 , Al E Stewart  4 , Jamison B Tuttle  1 , Lawrence Updyke  1 , Patrick R Verhoest  1 , Liuqing Wei  3 , Qingyi Yang  1 , Yuao Zhu  2
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Free article

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

Dafydd R Owen et al. Science. .
Free article

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.

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