SBIR Phase I: Stress Pathway Inhibition Prevents COVID-19 Infection (COVID-19)

这项小型企业创新研究（SBIR）第一阶段项目的更广泛影响是寻求为弱势患者（包括老年人和患有癌症、高血压、糖尿病和肥胖症的额外风险的患者）开发一流、无毒、廉价和有效的COVID-19治疗方法。与正常细胞相比，这些条件对患病细胞产生高水平的压力。该项目利用了COVID-19使用与癌细胞用于生存相同的途径来增强病毒感染的见解;这一过程导致免疫系统减弱，从而使肿瘤细胞和病毒繁殖。 拟议的项目将通过探索这种生存途径如何增加COVID-19的传染性，削弱免疫系统并诱导肿瘤细胞抵抗力来创造创新的抗病毒疗法。它的用途可以扩展到其他新的靶点和疗法。这个SBIR第一阶段项目利用了关于肿瘤和病毒感染之间相似性的见解。该项目将促进一种新型抑制剂转化为一种生存因子，通过增加肿瘤存活率和增强病毒感染来持续阻止这些伤口愈合。这种新型抑制剂可以有效阻断COVID-19刺突蛋白与这种存活因子的结合，这种存活因子已被证明在癌症和其他炎性疾病导致的应激肺细胞上高度表达。该项目的目标是：1）证明拟议的COVID-19抑制剂可以阻断COVID-19感染应激肺细胞; 2）减少细胞因子表达，以减轻与COVID-19感染相关的细胞因子风暴; 3）预防免疫减弱; 4）抑制凝血病，以减轻“血块风暴”。该项目将使用标准的体外病毒感染性测定和体内免疫活性荷瘤小鼠模型，这些小鼠感染了致命的COVID-19菌株。总之，这些研究将证明，拟议的铅生存因子抑制剂可以显着减少附着，COVID的进入和复制-该奖项反映了NSF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进行评估，被认为值得支持的搜索.

The broader impact of this Small Business Innovation Research (SBIR) Phase I project is the pursuit of developing a first-in-class, non-toxic, inexpensive, and effective treatment for COVID-19 for vulnerable patients including the elderly and those at additional risk from cancer, high blood pressure, diabetes and obesity. These conditions produce high levels of stress on diseased cells compared to normal cells. This project leverages insights that COVID-19 uses the same pathway to enhance viral infection as cancer cells use for survival; this process causes immune system weakening which allows tumor cells and viruses to multiply. The proposed project will create innovative anti-viral therapies by exploring how this survival pathway increases COVID-19 infectivity, weakens the immune system and induces tumor cell resistance. Its use can be expanded to other new targets and therapies. This SBIR Phase I project leverages insights regarding similarities between tumors and viral infections. This project will advance translation of a novel inhibitor to a survival factor that continually keeps these wounds from healing by increasing tumor survival and enhancing viral infections. This novel inhibitor can potently block the binding of COVID-19 spike protein to this survival factor, which has been shown to be highly expressed on stressed lung cells as a result of cancer and other inflammatory diseases. The goals of this project are to 1) show that the proposed COVID-19 inhibitor can block COVID-19 infection of stressed lung cells; 2) reduce cytokine expression to lessen the cytokine storm associated with COVID-19 infection; 3) prevent immune weakening and 4) inhibit coagulopathy to lessen the “blood clot storm”. The project will use standard in vitro viral infectivity assays and in vivo immune competent tumor-bearing mice models infected with a lethal strain of COVID-19. Together, these studies will demonstrate that the proposed lead survival factor inhibitor can significantly reduce the attachment, entry and replication of COVID-19 virus as well as reduce the immune suppressive nature of infected lung alveolar epithelial cells in vitro and in vivo.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.