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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-for-ChemRxiv.pdf (1.99 MB)

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

submitted on 14.05.2020, 12:03 and posted on 19.05.2020, 16:31 by Alex Zhavoronkov, Bogdan Zagribelnyy, Alexander Zhebrak, Vladimir Aladinskiy, Victor Terentiev, Quentin Vanhaelen, Dmitry S. Bezrukov, Daniil Polykovskiy, Rim Shayakhmetov, Andrey Filimonov, Michael Bishop, Steve McCloskey, Edgardo Leija, Deborah Bright, Keita Funakawa, Yen-Chu Lin, Shih-Hsien Huang, Hsuan-Jen Liao, Alex Aliper, Yan Ivanenkov

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​Medicinal chemistry VR analysis was provided by ​Nanome team and the video of VR session is available at ​​


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Insilico Medicine


Hong Kong

ORCID For Submitting Author


Declaration of Conflict of Interest

Insilico Medicine is a company developing an AI-based end-to-end integrated pipeline for drug discovery and development and engaged in aging and cancer research. Nanome is a company developing VR tools for scientific research and visualisation.