Discovery of inhibitors of Zika virus

项目摘要 寨卡病毒（ZIKV）的新型抑制剂是迫切需要的，以防止病毒诱导的寨卡病毒（ZIKV）的发生。 小头畸形和格林-巴利综合征。第一阶段SBIR可行性研究的目的是确定 特异性抑制ZIKV复制的药物样化合物。在第一阶段融资期间， 我们将对10万种具有最佳药物性质的化合物库进行命中发现活动。 将对试验中出现的质量命中进行后续检测，以研究效价， 选择性和作用机制。这些化合物中最令人感兴趣的将受到药用 化学驱动的命中导致探索结构-活性关系（SAR）。该项目的总体目标是 发现一个或多个新的先导化合物系列，其被定义为一种化学型抑制剂， 易于处理的SAR、针对可用ZIKV毒株的有效抗病毒活性和最小的细胞毒性。成功 这些努力将引发提交第二阶段的申请，这将推动该计划从早期 从优化到候选人选择。

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.