SBIR Phase I: Antiviral and Anti-inflammatory Live Biotherapeutics (COVID-19)

SBIR 第一阶段：抗病毒和抗炎活生物治疗药物 (COVID-19)

• 批准号: 2031154
• 负责人: Yiannis Kaznessis
• 金额: $ 25.6万
• 依托单位: General Probiotics 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: 2020-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2031154&HistoricalAwards=false
• 关键词: SBIR; Phase; Antiviral; Anti; inflammatory

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is the development of new therapeutics against coronavirus SARS-CoV-2 and associated COVID-19. Few broad-spectrum antivirals exist, and vaccines are effective but strain-specific and require development time for each new strain. This project will engineer probiotics native to the upper respiratory tract of humans to serve as antiviral and antibacterial agents. These probiotics will inhibit viral entry inside human lung cells and stop lung inflammation that causes lethal severe acute respiratory distress in COVID-19 patients. This development will be enabled by modern synthetic biology techniques and an agile research and development paradigm.This Small Business Innovation Research Phase I project will advance the development of new probiotics. These benign, non-virulent microbes will be equipped with defensins, protegrins and compstatins. Defensins are peptides known to inhibit critical steps in viral infection, including the antagonistic binding of angiotensin converting enzyme 2, the human cell receptor thought to facilitate Covid-19 entry inside lung epithelial cells. Protegrins are broad spectrum antimicrobials, with strong activity against bacteria, such as pneumonia-causing Klebsiella spp. and viral particles, including enveloped viruses like SARS-CoV-2. Compstatin is a complement system inhibitor that modulates the overactivation of inflammatory responses, which in the case of a coronavirus infection results in severe acute respiratory syndrome. At the end of this project, a library of live biotherapeutics will be developed that can exhibit antiviral, antibacterial and anti-inflammatory activity when expressing and secreting combinations of peptides.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.

该小企业创新研究 (SBIR) 第一阶段项目的更广泛影响/商业潜力是开发针对冠状病毒 SARS-CoV-2 和相关 COVID-19 的新疗法。几乎没有广谱抗病毒药物，疫苗虽然有效，但具有毒株特异性，并且每种新毒株都需要开发时间。该项目将改造人类上呼吸道原生的益生菌，作为抗病毒和抗菌剂。 这些益生菌将抑制病毒进入人体肺细胞，并阻止导致 COVID-19 患者致命的严重急性呼吸窘迫的肺部炎症。这一发展将通过现代合成生物学技术和敏捷的研发范式来实现。这个小型企业创新研究第一阶段项目将推动新型益生菌的开发。这些良性、无毒力的微生物将配备防御素、保护蛋白和坎普他汀。防御素是已知可抑制病毒感染中关键步骤的肽，包括血管紧张素转换酶 2 的拮抗结合，血管紧张素转换酶 2 是一种人类细胞受体，被认为有助于 Covid-19 进入肺上皮细胞内部。 Protegrin 是广谱抗菌剂，对细菌（例如引起肺炎的克雷伯菌属）具有很强的活性。和病毒颗粒，包括 SARS-CoV-2 等包膜病毒。坎普他汀是一种补体系统抑制剂，可调节炎症反应的过度激活，在冠状病毒感染的情况下，炎症反应会导致严重的急性呼吸综合征。在该项目结束时，将开发出一个活体生物治疗药物库，在表达和分泌肽组合时可以表现出抗病毒、抗菌和抗炎活性。该奖项反映了 NSF 的法定使命，并通过使用评估被认为值得支持基金会的智力价值和更广泛的影响审查标准。