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.

Discovery of SARS-CoV-2 main protease inhibitors using a synthesis-directed de novo design model

Aaron Morris, William McCorkindale, the COVID Moonshot Consortium, Nir Drayman, John D Chodera, Savaş Tay, Nir London, and Alpha A. Lee.
Chemical Communications 57:5909, 2021
[DOI]

We show how a machine learning models of ligand affinity can be coupled to synthetic enumeration models to rapidly generate potent inhibitors of the SARS-CoV-2 main viral protease.