STTR Phase I: Microbial Discovery and Biosynthesis of Targeted Protease Inhibitors (COVID-19)

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) Phase 1 project is to develop new lead compounds for treating COVID-19 by using microbial systems. The microbial assembly approach, which enables rapid, fermentation-based scale-up of therapeutic candidates for pre-clinical studies and early human trials, could accelerate the pace and reduce the cost of therapeutic development. Broad-spectrum therapeutics for COVID-19 could shorten hospital stays, reduce disease-associated mortality and morbidity, and help combat future coronavirus diseases. This Small Business Technology Transfer (STTR) Phase 1 project will use engineered microbial systems to identify and build antivirals for treating COVID-19. The approach departs from contemporary efforts to use microbial systems for the production of known, pharmaceutically relevant molecules by using them for the identification, evolution, and biosynthesis of new (or previously uncharacterized) biologically active agents. The research exploits contemporary approaches to synthetic biology to develop a microbial strain that detects inhibitors of enzymes needed for viral infection by SARS-CoV-2, and it will use that strain to (i) screen a library of late-stage pharmaceutical compounds for therapeutic candidates and (ii) build natural products that inhibit those enzymes. If successful, it will yield a set of therapeutic candidates for treating COVID-19 and a simple, easily shared microbial platform for screening compound libraries for targeted antivirals. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.