Zika virus (ZIKV), a mosquito-borne human flavivirus that causes microcephaly and other neurological disorders, has been a recent focus for the development of flavivirus vaccines and therapeutics. We report here a 4.0 Å resolution structure of the mature ZIKV in complex with ADI-30056, a ZIKV-specific human monoclonal antibody (hMAb) isolated from a ZIKV infected donor with a prior dengue virus infection. The structure shows that the hMAb interactions span across the E protein dimers on the virus surface, inhibiting conformational changes required for the formation of infectious fusogenic trimers similar to the hMAb, ZIKV-117. Structure-based functional analysis, and structure and sequence comparisons, identified ZIKV residues essential for neutralization and crucial for the evolution of highly potent E protein crosslinking Abs in ZIKV. Thus, this epitope, ZIKV’s “Achilles heel”, defined by the contacts between ZIKV and ADI-30056, could be a suitable target for the design of therapeutic antibodies.

中文翻译：

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在随后的黄病毒感染中寨卡病毒特异性中和的结构基础

寨卡病毒（ZIKV）是一种由蚊子传播的人类黄病毒，可引起小头畸形和其他神经系统疾病，最近一直是黄病毒疫苗和治疗剂开发的重点。我们在这里报告了与ADI-30056配合使用的成熟ZIKV的4.0Å分辨率结构，ADI-30056是从曾感染登革热病毒的ZIKV感染供体中分离出来的ZIKV特异性人单克隆抗体（hMAb）。该结构表明，hMAb相互作用跨越了病毒表面上的E蛋白二聚体，从而抑制了类似于hMAb ZIKV-117的传染性融合三聚体形成所需的构象变化。基于结构的功能分析以及结构和序列比较，确定了ZIKV残基对于中和至关重要，对于ZIKV中高效E蛋白交联Abs的进化至关重要。从而，