SBIR Phase I: AK-423: A broad-spectrum antiviral and immunomodulatory agent (COVID-19)

该小型企业创新研究（SBIR）第一阶段项目的更广泛影响/商业潜力源于针对当前COVID-19大流行的高效广谱抗病毒剂的开发。这种方法还可以解决未来其他病毒的爆发。该项目针对的是将出现多器官功能障碍的严重疾病的COVID-19患者群体。 这些患者需要ICU病房和呼吸机，其数量可能会使医疗保健系统不堪重负。该项目将开发一种抗病毒药物，以减轻社交距离措施并改善生活质量。这项小型企业创新研究（SBIR）第一阶段项目的重点是开发AK-423，这是一种潜在的有效抗COVID-19的抗病毒和免疫调节剂。技术目标侧重于检测AK-423（体外和体内）对COVID-19的抵抗力。最近的报告表明，COVID-19感染期间发生的多器官损伤的特征是指示细胞因子风暴的过度炎症反应、自身免疫和由复杂异常免疫反应引起的脓毒症综合征。理想的治疗方法不仅要抑制病毒复制，还要调节异常的免疫反应。AK-423针对病毒劫持的宿主代谢过程。它也是淋巴细胞分化的关键过程。抑制这种过程被证明可以抑制免疫应答，使免疫应答诱导的组织损伤最小化，抑制促炎细胞因子的产生，并有效地关闭病毒复制。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 stems from the development of an efficient broad-spectrum antiviral agent addressing the current COVID-19 pandemic. The approach can also address future outbreaks of other viruses. The project is targeting the group of COVID-19 patients who will develop severe illness featuring multiple organ dysfunction. Those patients need ICU units and ventilators in amounts that can overwhelm the health care system. This project will develop an antiviral agent to mitigate the social distancing measures and improve quality of life. This Small Business Innovation Research (SBIR) Phase I project focuses on the development AK-423, a potential efficient antiviral and immunomodulatory agent against COVID-19. The technical objectives focus on testing AK-423 (in-vitro and in-vivo) against COVID-19. Recent reports suggest that the multi-organ damage that occurs during COVID-19 infection is characterized by an exaggerated inflammatory response indicative of cytokine storm, auto-immunity, and a sepsis syndrome caused by complex abnormal immune reactions. An ideal treatment would not only suppress viral replication but would also regulate the abnormal immune response. AK-423 targets a host metabolic process that the virus hijacks. It is also a key process in the differentiation of lymphocytes. Inhibition of such process is proven to dampen the immune response, minimize immune response-induced tissue damage, inhibit production of pro-inflammatory cytokines, and efficiently shut down viral replication. This strategy will deliver an efficient broad-spectrum antiviral agent.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.