Development of novel isoflavone drugs as broad spectrum antivirals

 描述（由申请人提供）：基内塔发现了一类新型广谱小分子抗病毒药物，其通过宿主导向机制发挥作用。这些化合物已经证明了一种创新的作用机制，并靶向几种具有商业价值的高优先级病原体。基于先导色烯酮的候选物具有nM范围的效力，在体外和动物模型中抑制多种病毒，包括流感病毒、冠状病毒、西尼罗河病毒、埃博拉病毒和登革热病毒，具有有吸引力的药理学特征，并且在体内耐受良好。在这个应用程序中，我们将执行铅优化和 电极导线系列的临床前开发。该项目的主要里程碑是选择一种或多种提名的候选药物，用于正式的IND开发，以开发用于广泛呼吸道病毒感染的口服治疗药物。刺激宿主先天免疫应答的药物治疗作为治疗干预的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，我们的方法是在存在不同病毒的情况下刺激先天免疫， 对抗措施已经产生了有效对抗广泛的RNA和DNA病毒的有希望的线索。我们已经组建了一个高素质的开发团队，其中包括负责抗病毒发现工作的基内塔科学家和Michael Gale，Jr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.