JUL 14, 2021

SARS-CoV-2 main protease inhibitors: Physics-based approaches to the discovery of COVID-19 antivirals

Speaker:

Abba Leffler
Senior Principal Scientist

Abstract:

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. Worldwide, there have been over 240 million cases reported and close to 5 million deaths. Even though there are now several vaccines available for the disease, there is a clear need for the development of small molecule antivirals. One approach to the rapid discovery of such therapeutics is to apply physics-based methods to structures of the SARS-CoV-2 main protease, a key enzyme in the viral replication process. This talk will focus on the medicinal and computational chemistry driven discovery of main protease inhibitors. The challenges of coordinating this multi-company effort, the use of WaterMap to guide the design of inhibitors, and the use of Free-Energy Perturbation (FEP+) to predict the potencies of compounds to prioritize them for synthesis will be discussed. Biological results for key compounds will be presented.