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

STTR 第一阶段：微生物发现和靶向蛋白酶抑制剂的生物合成（COVID-19）

• 批准号: 2030347
• 负责人: Levi Kramer
• 金额: $ 25.59万
• 依托单位: THINK BIOSCIENCE, INC.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-15 至 2022-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2030347&HistoricalAwards=false
• 关键词: STTR; Phase; Microbial; Discovery; Biosynthesis

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.

该小企业技术转让 (STTR) 第一阶段项目的更广泛影响/商业潜力是开发新的先导化合物，用于利用微生物系统治疗 COVID-19。微生物组装方法能够快速、基于发酵地扩大治疗候选药物的规模，用于临床前研究和早期人体试验，可以加快治疗开发的步伐并降低治疗开发的成本。 COVID-19 的广谱疗法可以缩短住院时间，降低与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。该小型企业技术转让 (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。该方法不同于当代利用微生物系统来生产已知的药学相关分子的努力，即利用微生物系统来识别、进化和生物合成新的（或以前未表征的）生物活性剂。该研究利用现代合成生物学方法开发一种微生物菌株，可检测 SARS-CoV-2 病毒感染所需的酶抑制剂，并将使用该菌株来 (i) 筛选用于治疗的后期药物化合物库候选者和（ii）构建抑制这些酶的天然产品。如果成功，它将产生一系列治疗 COVID-19 的候选药物，以及一个简单、易于共享的微生物平台，用于筛选靶向抗病毒药物的化合物库。该奖项反映了 NSF 的法定使命，并通过使用基金会的评估进行评估，被认为值得支持。智力价值和更广泛的影响审查标准。