SBIR Phase II: Microbial Discovery and Biosynthesis of Targeted Protease Inhibitors (COVID-19)

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.