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

这项小企业创新研究（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。很少有广谱抗病毒药物存在，疫苗是有效的，但针对毒株，每种新毒株都需要开发时间。该项目将设计人类上呼吸道原生益生菌作为抗病毒和抗菌药物。这些益生菌将抑制病毒进入人体肺细胞，并阻止肺部炎症，而肺部炎症会导致COVID-19患者致命的严重急性呼吸窘迫。这一发展将由现代合成生物学技术和敏捷的研究和开发范式实现。这个小企业创新研究一期项目将推进新型益生菌的开发。这些良性的、无毒性的微生物将配备防御素、蛋白和压缩素。防御素是一种已知能抑制病毒感染关键步骤的肽，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是一种被认为能促进Covid-19进入肺上皮细胞的人类细胞受体。蛋白蛋白是广谱抗菌剂，对细菌（如引起肺炎的克雷伯氏菌）和病毒颗粒（包括SARS-CoV-2等包膜病毒）具有很强的活性。comp抑素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，将开发一个活的生物治疗药物库，当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 (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.