by Boby ML, Fearon D, Ferla M, Filep M, Koekemoer L, Robinson MC, The COVID moonshot consortium*, Chodera JD, Lee AA, London N, von Delft A, von Delft F. Science 2023, 382(6671): e075597. doi: 10.1126/science.abo7201
*including Perry B, Fraisse L, Sjö P, Boulet P, Hahn S, Mowbray C
Summary: The authors report the results of the ‘COVID Moonshot’, a fully open-science, crowdsourced, and structure-enabled drug discovery campaign targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease. They used crowdsourcing, machine learning, exascale molecular simulations, and high-throughput structural biology and chemistry to discover a noncovalent, nonpeptidic inhibitor scaffold with lead-like properties that is differentiated from current main protease inhibitors. They generated a detailed map of the structural plasticity of the SARS-CoV-2 main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. All compound designs, crystallographic data, assay, and molecules synthesized for this campaign were shared rapidly and openly, creating a rich, open, and intellectual property–free knowledge base for future anticoronavirus drug discovery.
