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

这个小企业创新研究第二阶段项目的更广泛的影响/商业潜力是开发一种成熟的、面向市场的方法，用于构建有针对性的、易于合成的病毒蛋白酶抑制剂。该技术将把发现平台扩展到新的靶点和疾病适应症，并为将临床前项目推进到有希望的线索建立生化基础，从治疗COVID-19的有效候选先导开始。该项目旨在产生涵盖发现平台和有前途的小分子的新知识产权，并将支持与制药公司在抗病毒治疗方面合作的新机会，这仍然是一个重要的未满足的医疗需求。这个小型企业创新研究二期项目旨在扩大和产业化该公司最近展示的方法，使用微生物系统来指导蛋白酶抑制剂的发现和组装。该项目重点关注COVID-19和其他缺乏有效治疗、具有重大流行潜力和/或与美国生物防御相关的病毒性疾病。该研究项目可能会发现一系列广泛的病毒蛋白酶抑制剂，并为靶向抑制剂筛选大量的生物合成途径库。该解决方案通过开发治疗COVID-19的强有力的主要候选药物和对已确定的hit进行（生物）合成优化的一般工作流程，对多部分工作进行了补充。这些任务的成功可能会扩展合成生物学的现代方法，将它们应用于新的生物活性化合物的发现和组装，并可能开发一个支持（生物）合成工作流程-一个结合应用酶学和合成化学的工作流程。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.