2015年底，寨卡病毒（ZIKV）在全世界范围内传播扩散，引发新生儿小头症和成人神经系统并发症，引起了世界卫生组织的高度关注，2016年WHO将其列为全球紧急公共卫生事件。ZIKV全病毒颗粒的原子结构很快得以解析（由本申请人作为共一作者研究于2016年4月发表在Science上），但是目前针对ZIKV的疫苗和抗病毒药物仅处于实验室研究阶段，仍然需要深入的科学研究。 研究表明，小分子多肽Z2可以抑制ZIKV感染活性。在本项目中，为了理解Z2多肽抑制病毒活性的机制，申请人将对Z2-ZIKV复合物进行结构研究。目前，我们已经解析了Z2-ZIKV的冷冻电镜结构，预实验结果发现Z2不仅可以有效抑制，甚至可以灭活寨卡病毒。而且，Z2多肽灭活寨卡病毒颗粒（Z2-ZIKV）表现出良好的免疫原性和免疫活性。基于此，我们将继续合成一系列Z2多肽类似物，综合冷冻电镜及生物化学方法深入研究多肽的抑制、灭活机制。

The rapid spread of Zika virus (ZIKV) and its unexpected symptom to birth defects and an autoimmune neurological syndrome have generated worldwide concern. This led the World Health Organization in February 2016 to declare “a public health emergency of.international concern”. The first atomic structure was resolved at 3.8 angstrom resolution of mature Zika virus, determined by cryo–electron microscopy (cryo-EM, contributed by Applicant as co-first author, published on Science in 2016). However, ZIKV vaccine development and specific drug study are just under research..It was reported that Z2 peptide could inhibit the infectivity of ZIKV. This proposal aims at atomic level understanding of Z2 inhibition mechanisms, by investigating the Z2-ZIKV complex structure. Preliminary results have solved the 3D structure of Z2-ZIKV, which revealed that Z2 peptide would rather deactive ZIKV infection than just inhibit the infectivity of ZIKV. Furthermore, the induced Z2-ZIKV complex showed promising immunogenicity and immunoreactivity, making itself a good candidate for vaccine design. Based on these, we plan to synthesize a series of Z2 peptide analogues for screening toward inhibition and deactivation of ZIKV. We could also expect fundamental insights that we can learn from these Cryo-EM and biochemical result, to help us for vaccine design and antivirus drug development.