Augmented Discovery of Potential Inhibitors of SARS-CoV-2 3CL Protease

Cherkasov, Artem | $999,000

British Columbia University of British Columbia 2020 CIHR Operating Grant

The COVID‑19 epidemic is causing serious or even fatal respiratory tract infections around the city of Wuhan, China and other countries. The urgent situation is pressing the global community to respond rapidly together to develop a vaccine or small molecule drug to inhibit viral infection. We have recently established a powerful Deep-Learning accelerated Docking pipeline to virtually screen a commercial 1.3-billion-compound library in a matter of one week–compared to the three years with previous programs. We have applied this novel algorithm to identify 1000 quality “candidate” compounds to inhibit the SARS-CoV-2 main protease (3CLpro) which is uniquely critical for the viral life cycle. We will screen these compounds with a high throughput screening biochemical assay and then evaluate these hits using a cell-based SARS-CoV-2 viral replication assay in a Canadian Containment Level 3 facilty at University of British Columbia. In addition we will use X-ray crystallography to refine the protease 3D crystal structure to accelerate the development of COVID‑19 therapeutic drug development. Our research program will significantly contribute to global response to the COVID‑19 outbreak by rapidly identifying small anti-viral drug molecules in an extremely condensed timeframe. Our expertise, facilities, and capabilities in cutting-edge Artificial Intelligence, inhibitor modeling, X-ray crystallography, coronavirus protease inhibition, human viral pathogen research, and anti-viral therapeutics are world class. Our first application this month of “Deep Docking” enabled the screening of 1.3B commercially available compounds against the essential SARS-CoV-2 protease, in 1 week compared to the 3 years of conventional docking. This accomplishment coupled with fast tracking anti-viral assays at UBC and high resolution 3D structure characterization provide our team, Canadians and global colleagues an enormous head start on developing an anti-viral therapeutic for COVID‑19

With funding from the Government of Canada

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