Nature：破解寨卡病毒秘密！解析寨卡病毒结构并鉴定药物... - 中国病毒学论坛|我们一直在坚持！

这些发现揭示出ZIKV病毒结构，并且鉴定出这种病毒表面上的潜在药物靶向作用位点。这一认识将有助全世界努力抵抗这种知之甚少的病毒。当前，ZIKV是公共卫生和研究的重点。

Duke-NUS副教授Shee-Mei Lok和她的研究团队利用低温电子显微技术分析大量纯化的ZIKV病毒颗粒，并且捕获这种病毒的图片。通过使用上千张图片，他们重建出ZIKV的高分辨率低温电子显微结构。

这种高分辨率结构表明这个病毒的整体结构类似于其他的黄病毒科病毒，如西尼罗病毒和登革热病毒。然而，研究人员发现ZIKV要比登革热病毒具有更大的热稳定性，而且即便在40℃---模拟在ZIKV感染后高烧患者的体温---下孵育时，在结构上也是稳定的。

这种结构也揭示出相比于登革热病毒，ZIKV表面蛋白具有更紧密的相互作用，因此使得它比登革热病毒更加稳定。这或许可以解释它能够在诸如精子、唾液和尿液之类的严峻环境中存活下来。除了通过被感染的蚊子叮咬进行传播外，这种病毒的结构稳定性使得它具有更强的适应性，这可能解释它具有通过性接触进行传播的特殊能力。类似的病毒，如西尼罗病毒和登革热病毒，不能够通过性接触进行传播。

总体而言，这些发现提示着让ZIKV结构去稳定化的抗体或药物可能有助降低这种病毒传染病的严重性，或者限制它的扩散。（Nature, 19 May 2016, doi:10.1038/nature17994）

Zika virus (ZIKV), formerly a neglected pathogen, has recently been associated with microcephaly in fetuses1, and with Guillian–Barré syndrome in adults2. Here we present the 3.7 Å resolution cryo-electron microscopy structure of ZIKV, and show that the overall architecture of the virus is similar to that of other flaviviruses. Sequence and structural comparisons of the ZIKV envelope (E) protein with other flaviviruses show that parts of the E protein closely resemble the neurovirulent West Nile and Japanese encephalitis viruses, while others are similar to dengue virus (DENV). However, the contribution of the E protein to flavivirus pathobiology is currently not understood. The virus particle was observed to be structurally stable even when incubated at 40 °C, in sharp contrast to the less thermally stable DENV3. This is also reflected in the infectivity of ZIKV compared to DENV serotypes 2 and 4 (DENV2 and DENV4) at different temperatures. The cryo-electron microscopy structure shows a virus with a more compact surface. This structural stability of the virus may help it to survive in the harsh conditions of semen4, saliva5 and urine6. Antibodies or drugs that destabilize the structure may help to reduce the disease outcome or limit the spread of the virus.