Discovery of SARS-CoV-2 main protease inhibitors using a synthesis-directed <i>de novo</i> design model
Aaron Morris, William McCorkindale, The COVID Moonshot Consortium, Nir Drayman, John D. Chodera, Savaş Tay, Nir London, Alpha A. Lee
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.
Topics & Concepts
ProteaseSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Coronavirus disease 2019 (COVID-19)2019-20 coronavirus outbreakComputational biologyChemistryVirologyCombinatorial chemistryEnzymeBiologyStereochemistryBiochemistryMedicineInfectious disease (medical specialty)DiseasePathologyOutbreakComputational Drug Discovery MethodsSynthesis and biological activityClick Chemistry and Applications