SBIR-STTR Award

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.

The broader impact/commercial potential of this Small Business Innovation Research Phase II project is to develop a mature, market-ready approach for building targeted, readily synthesizable inhibitors of viral proteases. The technology will extend the discovery platform to new targets and disease indications and build a biochemical foundation for progressing preclinical programs to promising leads, starting with a potent lead candidate for treating COVID-19. The project seeks to generate new intellectual property that covers the discovery platform and promising small molecules, and it will support new opportunities to partner with pharmaceutical companies on antiviral therapeutics, which continue to be an important unmet medical need. This Small Business Innovation Research Phase II project seeks to expand and industrialize the company?s recently demonstrated approach for using microbial systems to guide the discovery and assembly of protease inhibitors. The project focuses on COVID-19 and other viral diseases that lack effective treatments, exhibit significant epidemic potential, and/or remain relevant to U.S. biodefense. The research program may uncover inhibitors of a broad set of viral proteases and as it screens large libraries of biosynthetic pathways for targeted inhibitors. This solution complements the multi-part effort by developing a potent lead candidate for treating COVID-19 and a general workflow for the (bio)synthetic optimization of hits identified. Success in these tasks may stretch contemporary approaches to synthetic biology by applying them to the discovery and assembly of new biologically active compounds and may develop a supporting (bio)synthetic workflow?one that that combines applied enzymology and synthetic chemistry.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.