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.

A white-knuckle ride of open COVID drug discovery

Frank von Delft, Mark Calmiano, John Chodera, Ed Griffen, Alpha Lee, Nir London, Tatiana Matviuk, Ben Perry, Matt Robinson, and Annette von Delft.
Nature 594:330, 2021.
[DOI] [PDF]

The COVID Moonshot is an open science effort to discover a direct-acting SARS-CoV-2 oral antiviral. Here, we share lessons from this effort, including the missed opportunity to develop a phase 2 ready drug more than a decade ago that could have halted the COVID-19 pandemic in its tracks.

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.

Crowdsourcing drug discovery for pandemics

John D. Chodera, Alpha A. Lee, Nir London, and Frank von Delft.
Nature Chemistry 12:581, 2020
[DOI] [PDF] [COVID Moonshot] [GoFundMe]

The COVID-19 pandemic has left the world scrambling to find effective therapies to stem the tidal wave of death and put an end to the worldwide disruption caused by SARS-CoV-2. In this Correspondence, we argue for the need for a new open, collaborative drug discovery model (exemplified by our COVID Moonshot collaboration) that breaks free of the limitations of industry-led competitive drug discovery efforts that necessarily restrict information flow and hinder rapid progress by prioritizing profits and patent protection over human lives.