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

ABSTRACT: The SARS-CoV-2 main viral protease (Mpro) is an attractive target for antivirals given its distinctiveness from host proteases, essentiality in the viral life cycle and conservation across coronaviridae. We launched the COVID Moonshot initiative to rapidly develop patent-free antivirals with open science and open data. Here we report the use of machine learning for de novo design, coupled with synthesis route prediction, in our campaign. We discover novel chemical scaffolds active in biochemical and live virus assays, synthesized with model generated routes.

SUBMITTER: Morris A

PROVIDER: S-EPMC8204246 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Discovery of SARS-CoV-2 main protease inhibitors using a synthesis-directed <i>de novo</i> design model.

Morris Aaron A McCorkindale William W Consortium The Covid Moonshot TCM Drayman Nir N Chodera John D JD Tay Savaş S London Nir N Lee Alpha A AA

Chemical communications (Cambridge, England) 20210601 48

The SARS-CoV-2 main viral protease (Mpro) is an attractive target for antivirals given its distinctiveness from host proteases, essentiality in the viral life cycle and conservation across coronaviridae. We launched the COVID Moonshot initiative to rapidly develop patent-free antivirals with open science and open data. Here we report the use of machine learning for de novo design, coupled with synthesis route prediction, in our campaign. We discover novel chemical scaffolds active in biochemical ...[more]

PMID: 34008627

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