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、市场准备好的方法，以建立有针对性的、易于合成的病毒蛋白酶抑制剂。这项技术将把发现平台扩展到新的靶点和疾病适应症，并为将临床前项目进展为有前景的线索奠定生物化学基础，从治疗新冠肺炎的有效候选药物开始。该项目寻求产生新的知识产权，涵盖发现平台和前景看好的小分子，并将支持与制药公司在抗病毒疗法上合作的新机会，这仍然是一个重要的未得到满足的医疗需求。这个小企业创新研究第二阶段项目寻求扩大该公司最近展示的使用微生物系统来指导发现和组装蛋白酶抑制剂的方法并将其产业化。该项目专注于新冠肺炎和其他缺乏有效治疗、表现出显著的流行潜力和/或仍与美国生物防御相关的病毒性疾病。该研究计划可能会发现广泛的病毒蛋白水解酶的抑制剂，并在筛选靶向抑制剂的生物合成途径的大型文库时。该解决方案通过开发用于治疗新冠肺炎的强有力的领先候选药物和用于(生物)已识别命中优化的通用工作流程，补充了多部分工作。这些任务的成功可能会延伸当代合成生物学的方法，将它们应用于新的生物活性化合物的发现和组装，并可能开发出支持(生物)合成工作流程-结合应用酶学和合成化学。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.