寨卡病毒 NS5 结构揭示了一个保守的结构域构象。

Department of Biochemistry, University of California, Riverside, Riverside, California 92521, USA.

Department of Plant Pathology and Microbiology, University of California, Riverside, Riverside, California 92521, USA.

Nat Commun. 2017 Mar 27;8:14763. doi: 10.1038/ncomms14763.

The recent outbreak of Zika virus (ZIKV) has imposed a serious threat to public health. Here we report the crystal structure of the ZIKV NS5 protein in complex with S-adenosyl-L-homocysteine, in which the tandem methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains stack into one of the two alternative conformations of flavivirus NS5 proteins. The activity of this NS5 protein is verified through a de novo RdRp assay on a subgenomic ZIKV RNA template. Importantly, our structural analysis leads to the identification of a potential drug-binding site of ZIKV NS5, which might facilitate the development of novel antivirals for ZIKV.

寨卡病毒（ZIKV）的近期爆发对公共卫生构成了严重威胁。在这里，我们报告了寨卡病毒 NS5 蛋白与 S-腺苷-L-同型半胱氨酸复合物的晶体结构，其中串联甲基转移酶（MTase）和 RNA 依赖性 RNA 聚合酶（RdRp）结构域堆叠成黄病毒 NS5 蛋白的两种替代构象之一。通过在亚基因组 ZIKV RNA 模板上进行从头 RdRp 测定，验证了该 NS5 蛋白的活性。重要的是，我们的结构分析导致鉴定出寨卡病毒 NS5 的一个潜在药物结合位点，这可能有助于开发针对寨卡病毒的新型抗病毒药物。