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

小企业创新研究第一阶段项目的更广泛影响/商业潜力源于开发一种应对当前新冠肺炎大流行的高效广谱抗病毒剂。该方法还可以应对未来爆发的其他病毒。该项目针对的是新冠肺炎患者群体，他们将患上以多器官功能障碍为特征的严重疾病。这些患者需要ICU病房和呼吸机，其数量可以使医疗保健系统不堪重负。该项目将开发一种抗病毒药物，以缓解社会疏远措施，提高生活质量。这个小企业创新研究第一阶段的项目专注于开发AK-423，一种潜在的高效抗病毒和免疫调节剂，对抗新冠肺炎。技术目标集中在测试AK-423(体外和体内)对新冠肺炎的作用。最近的报道表明，新冠肺炎感染期间发生的多器官损害的特征是过度的炎症反应，表明细胞因子风暴、自身免疫和由复杂的异常免疫反应引起的脓毒症综合征。理想的治疗方法不仅能抑制病毒复制，还能调节异常的免疫反应。AK-423针对的是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。抑制这一过程被证明可以抑制免疫反应，最大限度地减少免疫反应引起的组织损伤，抑制促炎细胞因子的产生，并有效地阻止病毒复制。这一战略将提供一种高效的广谱抗病毒药物。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.