Upadhyay Anup K, Cyr Matthew, Longenecker Kenton, Tripathi Rakesh, Sun Chaohong, Kempf Dale J
AbbVie Inc., 1 North Waukegan Road, North Chicago, IL 60064, USA.
Acta Crystallogr F Struct Biol Commun. 2017 Mar 1;73(Pt 3):116-122. doi: 10.1107/S2053230X17001601. Epub 2017 Feb 21.
The rapid spread of the recent Zika virus (ZIKV) epidemic across various countries in the American continent poses a major health hazard for the unborn fetuses of pregnant women. To date, there is no effective medical intervention. The nonstructural protein 5 of Zika virus (ZIKV-NS5) is critical for ZIKV replication through the 5'-RNA capping and RNA polymerase activities present in its N-terminal methyltransferase (MTase) and C-terminal RNA-dependent RNA polymerase (RdRp) domains, respectively. The crystal structure of the full-length ZIKV-NS5 protein has been determined at 3.05 Å resolution from a crystal belonging to space group P222 and containing two protein molecules in the asymmetric unit. The structure is similar to that reported for the NS5 protein from Japanese encephalitis virus and suggests opportunities for structure-based drug design targeting either its MTase or RdRp domain.
近期寨卡病毒（ZIKV）疫情在美洲各国迅速蔓延，对孕妇腹中胎儿构成重大健康威胁。迄今为止，尚无有效的医学干预措施。寨卡病毒非结构蛋白5（ZIKV-NS5）分别通过其N端甲基转移酶（MTase）和C端RNA依赖的RNA聚合酶（RdRp）结构域中的5'-RNA加帽和RNA聚合酶活性，对ZIKV复制至关重要。已从属于空间群P222且不对称单元中含有两个蛋白质分子的晶体，以3.05 Å分辨率确定了全长ZIKV-NS5蛋白的晶体结构。该结构与日本脑炎病毒NS5蛋白的报道结构相似，为针对其MTase或RdRp结构域进行基于结构的药物设计提供了机会。
