Discovery of inhibitors of Zika virus

项目总结 目前迫切需要新型寨卡病毒抑制剂(ZIKV)来预防病毒诱导的寨卡病毒感染 小头畸形和格林-巴利综合征。这项第一阶段SBIR可行性研究的目标是确定 专门抑制ZIKV复制的类药物化合物。在本第一阶段资助期内， 我们将对10万个具有最佳类药物特性的化合物库进行匹配查找活动。 从化验中产生的高质量命中将接受后续测试，以调查其效力， 选择性和作用机理。其中最有趣的化合物将受到药物的影响 化学驱动的点击到领先的探索结构-活性关系(SAR)。这个项目的总体目标是 发现一个或多个新的铅系列，它被定义为一种化学型抑制物，它证明了 易处理的SAR，强大的抗病毒活性，对现有的ZIKV毒株和最低的细胞毒性。在以下方面取得成功 这些努力将触发第二阶段申请的提交，这将使该计划从早期开始 将优化带入候选人选择。

PROJECT SUMMARY Novel inhibitors of Zika virus (ZIKV) are urgently needed to prevent the occurrence of virus-induced microcephaly and Guillain-Barré syndrome. The objective of this Phase I SBIR feasibility study is to identify drug-like compounds that specifically inhibit ZIKV replication. During the course of this Phase I funding period, we will execute hit finding campaign against a library of 100,000 compounds with optimal drug-like properties. Quality hits that emerge from the assay will be subjected to follow-on testing that will investigate the potency, selectivity, and mechanism of action. The most interesting of these compounds will be subjected to medicinal chemistry driven hit-to-lead to explore structure-activity relationships (SAR). The overall goal of this project is to discover one or more novel lead series which is defined as a chemotype inhibitor that demonstrates tractable SAR, potent antiviral activity against the available ZIKV strains and minimal cytotoxicity. Success in these endeavors will trigger the submission of a Phase II application that will advance the program from Early Lead Optimization through to Candidate Selection.