Department of Biochemistry, University of California, Riverside, CA, 92521, USA.
Department of Microbiology and Plant Pathology , University of California, Riverside, CA, 92521, USA.
Cell Mol Life Sci. 2018 May;75(10):1723-1736. doi: 10.1007/s00018-018-2751-x. Epub 2018 Feb 8.
Zika virus (ZIKV) belongs to the positive-sense single-stranded RNA-containing Flaviviridae family. Its recent outbreak and association with human diseases (e.g. neurological disorders) have raised global health concerns, and an urgency to develop a therapeutic strategy against ZIKV infection. However, there is no currently approved antiviral against ZIKV. Here we present a comprehensive overview on recent progress in structure-function investigation of ZIKV NS5 protein, the largest non-structural protein of ZIKV, which is responsible for replication of the viral genome, RNA capping and suppression of host interferon responses. Structural comparison of the N-terminal methyltransferase domain and C-terminal RNA-dependent RNA polymerase domain of ZIKV NS5 with their counterparts from related viruses provides mechanistic insights into ZIKV NS5-mediated RNA replication, and identifies residues critical for its enzymatic activities. Finally, a collection of recently identified small molecule inhibitors against ZIKV NS5 or its closely related flavivirus homologues are also discussed.
Zika 病毒（ZIKV）属于正链单链 RNA 含有的黄病毒科。其最近的爆发以及与人类疾病（如神经紊乱）的关联引发了全球健康关注，并迫切需要开发针对 ZIKV 感染的治疗策略。然而，目前还没有针对 ZIKV 的批准抗病毒药物。本文对 Zika 病毒非结构蛋白 5（ZIKV NS5）的结构-功能研究进展进行了全面综述，ZIKV NS5 是 ZIKV 中最大的非结构蛋白，负责病毒基因组的复制、RNA 加帽和抑制宿主干扰素反应。ZIKV NS5 的 N 端甲基转移酶结构域和 C 端 RNA 依赖的 RNA 聚合酶结构域与相关病毒的对应结构域的结构比较为 ZIKV NS5 介导的 RNA 复制提供了机制见解，并确定了对其酶活性至关重要的残基。最后，还讨论了最近鉴定的针对 ZIKV NS5 或其密切相关的黄病毒同源物的小分子抑制剂。
