To receive the Zoom link, please send your name and affiliation to mphilipp@gc.cuny.edu.
Speaker: Nir London, Ph.D., The Alan and Laraine Fischer Career Development Chair, Department of Organic Chemistry, Weizmann Institute of Science
Title: Crowdsourcing a Cure for COVID-19
Abstract: COVID-19, caused by SARS-CoV-2, lacks effective therapeutics. Additionally, no antiviral drugs or vaccines were developed against the closely related coronavirus, SARS-CoV-1 or MERS-CoV, despite previous zoonotic outbreaks. To identify starting points for such therapeutics, we performed a large-scale screen of electrophile and non-covalent fragments through a combined mass spectrometry and X-ray approach against the SARS-CoV-2 main protease. The results with more than 71 co-crystal structures that span the entire active site, were released to the public and we implemented a crowd-sourcing platform to solicit next generation design ideas. Thousands of suggestions were submitted, of which we made and tested >1,500, through a global consortium including academic labs, chemical vendors, pharma advisors and more. This effort resulted in <100nM inhibitors with crystallographic confirmation and activity in live virus assays. Crowd computing (Folding@Home) was harnessed for compound optimization; AI (via PostEra) for prioritization and retrosynthesis. This is still an on-going live project that can benefit from the input of medicinal chemists world-wide. We hope this initiative can serve as a template for an alternative drug discovery pipeline for areas that are unappealing to traditional pharma such as pandemic preparedness and antibiotic development.