key: cord-0987036-i8x5v7bj
authors: Morris, Aaron; McCorkindale, William; Consortium, The COVID Moonshot; Drayman, Nir; Chodera, John D.; Tay, Savaş; London, Nir; Lee, Alpha A.
title: Discovery of SARS-CoV-2 main protease inhibitors using a synthesis-directed de novo design model
date: 2021-05-06
journal: Chemical communications
DOI: 10.1039/d1cc00050k
sha: c45fb32d7883eef6cf68a8a2a695f6564e2de5d7
doc_id: 987036
cord_uid: i8x5v7bj

The SARS-CoV-2 main viral protease (M(pro)) 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.

Chemical Shift (ppm) 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 

Spectrum RetTime: 0.963 Datafile: D:\DATA\2020\2007\200731B2257-29-P1J.lcd m/z

RetTime: 1.260 Datafile: D:\DATA\2020\2007\200731B2257-29-P1J.lcd m/z