A Platform Targeting Protein Structural Dynamics for High-Throughput Discovery of Small Molecule Antiviral Leads

Led by Joseph Muretta, research assistant professor, College of Biological Sciences, researchers in this study hypothesize that changes in the structural dynamics of SARS-CoV-2 proteins, detected by high-throughput time resolved fluorescence measurements of engineered biosensors of these proteins, will enable discovery of small molecule antiviral leads with potent effects on the virus life cycle. These leads will fuel the development of antiviral drugs to treat COVID-19 and future SARS related pandemics.

“We have established a workflow for the discovery of small molecules that alter the structural dynamics, and subsequently function, of interrogated protein,” said Muretta. “This approach has been used successfully to target an array of proteins with disease relevance to heart failure, cancer, Alzheimer's, aging, and muscular dystrophy. We propose to use this workflow now in the discovery of small molecule antiviral leads to treat COVID-19.”

This project is supported by the UMN Campus Public Health Officer's CO:VID (Collaborative Outcomes: Visionary Innovation & Discovery) grants program, which support University of Minnesota faculty to catalyze and energize small-scale research projects designed to address and mitigate the COVID-19 virus and its associated risks.