疹病毒的结构基础 普利特利维尔和阿米纳米维尔的形酶-原酶抑制
Andrey G Baranovskiy1, Qixiang He2, Yoshiaki Suwa1
1Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
Science advances
|November 7, 2025
概括
新的冷EM结构揭示了简单疹病毒的酶-原酶抑制剂pritelivir和amenamevir如何阻止病毒DNA复制. 这为开发针对疹病毒感染的新型抗病毒疗法提供了基础.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 药物发现 药物发现 药物发现
背景情况:
- 疹病毒感染很常见,并与各种疾病有关.
- 人类单纯疹病毒1型 (HSV-1) 的DNA复制取决于酶-原酶 (HP) 复合体.
- 惠普复合体是抗病毒药物开发的关键目标.
研究的目的:
- 为了阐明HP抑制剂的结合机制,pritelivir和amenamevir.
- 为HSV-1HP复合体的功能和抑制提供结构性见解.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定结构.
- 仅针对HSV-1HP复合体而获得结构,并与分叉DNA模板结合.
- 还确定了与普利特利维尔和阿梅纳维尔结合的复合物的结构.
主要成果:
- 冷EM结构揭示了HP复合体的双叶架构.
- 这些结构说明了HP在病毒DNA复制叉上的协调作用.
- 确定了普里特利维尔和阿米纳维尔在阻断酶活性中的精确结合部位和机制.
结论:
- 确定的结构为HP抑制提供了详细的结构基础.
- 了解这些机制对于设计针对HSV-1的改进抗病毒疗法至关重要.
- 这项研究为开发更有效的疹病毒感染治疗方法奠定了基础.
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