Nature:破解寨卡病毒秘密!解析寨卡病毒结构并鉴定药物靶向位点

2016-04-21 生物谷 梅斯医学

在一项新的研究中,来自杜克-新加坡国立大学医学院(Duke-NUS)的研究人员在理解寨卡病毒(ZIKV)结构方面取得重要突破。相关研究结果于2016年4月19日在线发表在Nature期刊上,论文标题为“Structure of the thermally stable Zika virus”。 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

在一项新的研究中,来自杜克-新加坡国立大学医学院(Duke-NUS)的研究人员在理解寨卡病毒(ZIKV)结构方面取得重要突破。相关研究结果于2016年4月19日在线发表在Nature期刊上,论文标题为“Structure of the thermally stable Zika virus”。

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。(进一步阅读:Science:首次解析出寨卡病毒三维结构

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。

Lok说,“这是令人兴奋的,这是因为我们的结构将给世界各地正在努力发现抵抗ZIKV的治疗试剂的其他研究人员提供重要线索。”

“此外,我们已证实ZIKV具有不同于来自同一个病毒科的影响大脑的其他病毒(如西尼罗病毒)的独特结构,而且也具有不同于导致发热的那些病毒(如登革热病毒)的独特结构。能够让这些结构发生突变以便更好地理解它们如何影响ZIKV感染人类,而且也能够潜在地导致人们开发出一种安全的降低这些副作用的疫苗。”

Lok的下一步就是理解强效抗体对ZIKV的影响。通过研究这项研究中提供的结构,她的团队将努力确定这些抗体如何可能被用来杀死这种病毒。他们也希望鉴定出哪些强效抗体可能能够在紧急情况下用于治疗病人,如ZIKV传染病突然暴发或者妊娠期间感染ZIKV的情形下。

ZIKV导致寨卡病毒病,其常见症状为轻度发烧、皮疹、结膜炎、肌肉和关节疼痛、虚弱或头疼。

今年2月,世界卫生组织宣布寨卡病毒传播是“一种引起国际关注的公共卫生紧急事态”。科学家们已发现这种病毒与胎儿小头畸形(microcephaly)和成年人格林-巴利综合征(Guillain-Barré syndrome)相关联。

原始出处:

Victor A. Kostyuchenko, Elisa X. Y. Lim,et al,Structure of the thermally stable Zika virus,Nature,24 March 2016 

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    2016-08-16 hongbochen
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    2016-05-19 liye789132251
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    2016-04-21 hekzn

    学习了长知识

    0