Zika virus (ZIKV) infection, which initially was endemic only in Africa and Asia, is rapidly spreading throughout Europe, Oceania, and the Americas. Although there have been enormous efforts, there is still no approved drug to treat ZIKV infection. Herein, we report the synthesis and biological evaluation of agents with noncompetitive mechanism of the ZIKV NS2B/NS3 protease inhibition through the binding to an allosteric site. Compounds 1 and 2 showed potent activity in both enzymatic and cellular assays. Derivative 1 efficiently reduced the ZIKV protein synthesis and the RNA replication and prevented the mice from life-threatening infection and the brain damage caused by ZIKV infection in a ZIKV mouse model.

中文翻译：

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发现可防止小鼠受到威胁生命的感染和脑损伤的寨卡病毒 NS2B/NS3 抑制剂

寨卡病毒 (ZIKV) 感染最初仅在非洲和亚洲流行，现在正在欧洲、大洋洲和美洲迅速蔓延。尽管付出了巨大的努力，但仍然没有批准的药物来治疗 ZIKV 感染。在此，我们报告了通过与变构位点结合来抑制 ZIKV NS2B/NS3 蛋白酶的非竞争机制的药物的合成和生物学评估。化合物1和2在酶促和细胞测定中均显示出有效的活性。在 ZIKV 小鼠模型中，衍生物1有效地减少了 ZIKV 蛋白合成和 RNA 复制，并防止小鼠受到威胁生命的感染和 ZIKV 感染引起的脑损伤。