Development of novel isoflavone drugs as broad spectrum antivirals

 描述(申请人提供)：Kineta发现了一类通过宿主定向机制发挥作用的新型广谱小分子抗病毒药物。这些化合物展示了一种创新的作用机制，并针对几种具有商业价值的高优先级病原体。基于色满酮的主要候选化合物在NM范围内具有效力，在体外和动物模型中抑制包括流感、冠状病毒、西尼罗河病毒、埃博拉病毒和登革病毒在内的多种病毒，具有吸引人的药理特征，并且在体内具有良好的耐受性。在此应用程序中，我们将执行Lead优化和 铅系列的临床前开发。该项目的主要里程碑是选择一个或多个提名的候选药物进行正式的IND开发，以期开发出一种广泛的呼吸道病毒感染的口服疗法。激发宿主先天免疫反应的药物治疗作为治疗干预的一种策略越来越受到重视，并有可能重新定义抗病毒药物开发的范式。对有效的抗病毒药物的需求是巨大的，我们在各种病毒存在的情况下刺激先天免疫的方法 对策已经产生了对广泛的RNA和DNA病毒有效的有希望的线索。我们已经组建了一支高素质的开发团队，其中包括负责抗病毒发现工作的Kineta科学家和小迈克尔·盖尔教授。他是先天免疫和抗病毒反应方面的专家。

 DESCRIPTION (provided by applicant): Kineta has discovered a novel class of broad spectrum small molecule antivirals that function through a host directed mechanism. These compounds have demonstrated an innovative mechanism of action and target several high priority pathogens that are commercially valuable. The lead chromenone-based candidates have potency in the nM range, inhibit multiple viruses including influenza, coronavirus, West Nile, ebola, and dengue virus in vitro and in animal models, have an attractive pharmacologic profile, and are well tolerated in vivo. In this application, we will perform lead optimization and preclinical development of the lead series. The major milestone of the project is to select one or more nominated drug candidates for formal IND-enabling development towards an oral therapeutic for broad respiratory viral infections. Drug treatment to stimulate the host innate immune response is increasingly appreciated as a strategy for therapeutic intervention and has the potential to redefine the paradigm of antiviral drug development. The need for effective antivirals is great, and our approach to stimulate innate immunity in the presence of diverse viral countermeasures has yielded promising leads that are effective against a broad range of RNA and DNA viruses. We have assembled a highly qualified development team that includes the Kineta scientists responsible for the antiviral discovery work and Prof Michael Gale, Jr. of the University of Washington, an expert in innate immunity and the antiviral response.