Discovery of novel Henipavirus inhibitors

项目3--摘要 该项目的目标是发现新的埃尼帕病毒抑制剂。亨尼帕病毒是一种致命的空气传播呼吸道病毒 研究不足且知之甚少的病原体。迫切需要抗病毒治疗 用于预防大流行的埃尼帕病毒。我们将通过追求三个目标来实现这一目标。(I)筛选和 鉴定抑制Nipah和/或Hendra病毒的新化合物。因为尼帕和亨德拉病毒应该是 在BSL4处理，在高密封性下执行高通量筛分是具有挑战性的。要克服这一点 瓶颈，我们将使用BSL2雪松黑尼帕病毒作为抗病毒筛选的替代系统。从以下位置识别的命中 雪松海尼帕病毒检测将在BSL4设施的亨德拉和尼帕病毒中得到验证。(二)开发工具 化合物，确定目标蛋白质，并优化分子。(3)相关先导化合物的体外评价 和体内模型，并选择开发候选对象进行IND使能研究。建议的基于单元格的 方法可能会发现新的抗病毒靶点，而靶向抗病毒方法可能无法处理这些靶点。

PROJECT 3 – ABSTRACT The goal of this project is to discover novel henipavirus inhibitors. Henipavirus is a deadly airborne respiratory pathogen that are under-researched and poorly understood. Antiviral therapy is urgently needed for henipaviruses for pandemic preparedness. We will achieve the goal by pursuing three aims. (i) Screen and identify novel compounds for Nipah and/or Hendra virus inhibition. Since Nipah and Hendra viruses should be handled at BSL4, it is challenging to perform high-throughput screen at high containment. To overcome this bottleneck, we will use a BSL2 Cedar henipavirus as a surrogate system for antiviral screen. Hits identified from the Cedar henipavirus assay will be validated in Hendra and Nipah viruses at the BSL4 facility. (ii) Develop tool compounds, determine target protein, and optimize molecules. (iii) Evaluate lead compounds in relevant in vitro and in vivo models and select Development Candidate for IND-enabling studies. The proposed cell-based approach may discover novel antiviral targets that may not be tractable for target-based antiviral approach.