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。
