Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors

Boby ML, Fearon D, Ferla M, Filep M, Robinson MC, The COVID Moonshot Consortium, Chodera JD, Lee A, London N, von Delft F.
Science 382:eabo7201, 2023 [DOI] [PDF] [ready to use data]

We report the discovery of a new oral antiviral non-covalent SARS-CoV-2 main protease inhibitor developed by the COVID Moonshot, a global open science collaboration leveraging free energy calculations on Folding@home and ML-accelerated synthesis planning, now in accelerated preclinical studies funded by an $11M grant from the WHO ACT-A program via the Wellcome Trust. We are currently in discussions with generics manufacturers about partnering with us throughout clinical trials to ensure we can scale up production for global equitable and affordable access once approved by regulatory agencies.

Turning high-throughput structural biology into predictive inhibitor design

Saar KL, McCorkindale W, Fearon D, Boby M, Barr H, Ben-Shmuel A, COVID Moonshot Consortium, London N, von Delft F, Chodera JD, Lee AA
PNAS 120:e2214168120, 2023 [DOI]

We demonstrate how potent inhibitors can be predicted from high-throughput structural biology, demonstrating this approach against the SARS-CoV-2 main viral protease (Mpro).