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

这个小企业技术转让（STTR）第一阶段项目的更广泛影响/商业潜力是通过使用微生物系统开发用于治疗COVID-19的新先导化合物。微生物组装方法能够快速、基于发酵的扩大临床前研究和早期人体试验的候选治疗药物的规模，可以加快治疗药物开发的步伐并降低成本。COVID-19的广谱疗法可以缩短住院时间，降低疾病相关的死亡率和发病率，并有助于对抗未来的冠状病毒疾病。这个小企业技术转让（STTR）第一阶段项目将使用工程微生物系统来识别和构建用于治疗COVID-19的抗病毒药物。该方法背离了当代使用微生物系统生产已知的药学相关分子的努力，通过使用它们来鉴定，进化和生物合成新的（或以前未表征的）生物活性剂。该研究利用当代合成生物学方法开发了一种微生物菌株，该菌株可检测SARS-CoV-2病毒感染所需的酶抑制剂，并将使用该菌株（i）筛选治疗候选药物的晚期药物化合物库和（ii）构建抑制这些酶的天然产物。如果成功，它将产生一组治疗COVID-19的候选药物，以及一个简单、易于共享的微生物平台，用于筛选化合物库中的靶向抗病毒药物。该奖项反映了NSF的法定使命，并被认为值得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来支持。

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.