3 research outputs found
Potential Non-Covalent SARS-CoV-2 3C-like Protease Inhibitors Designed Using Generative Deep Learning Approaches and Reviewed by Human Medicinal Chemist in Virtual Reality
One of the most important SARS-CoV-2 protein targets for therapeutics is the 3C-like protease
(main protease, Mpro). In our previous work1​we used the first Mpro crystal structure to become
available, 6LU7. On February 4, 2020 Insilico Medicine released the first potential novel
protease inhibitors designed using a ​de novo,​AI-driven generative chemistry approach. Nearly
100 X-ray structures of Mpro co-crystallized both with covalent and non-covalent ligands have
been published since then. Here we utilize the recently published 6W63 crystal structure of
Mpro complexed with a non-covalent inhibitor and combined two approaches used in our
previous study: ligand-based and crystal structure-based. We published 10 representative
structures for potential development with 3D representation in PDB format and welcome
medicinal chemists for broad discussion and generated output analysis. The molecules in SDF
format and PDB-models for generated protein-ligand complexes are available here and at
https://insilico.com/ncov-sprint/.​Medicinal chemistry VR analysis was provided by ​Nanome team
and the video of VR session is available at ​https://bit.ly/ncov-vr.​
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