抗病毒药物布莱维尔提德与乙型肝炎和D型肝炎病毒受体蛋白NTCP结合的结构
Hongtao Liu1, Dariusz Zakrzewicz2, Kamil Nosol1
1Institute of Molecular Biology and Biophysics, ETH Zürich, Zürich, Switzerland.
Nature communications
|March 21, 2024
概括
布列维 (BLV) 通过与NTCP载体结合,阻止乙型肝炎和D型肝炎病毒的进入. 它的结构揭示了BLV如何抑制胆汁盐运输和病毒对接,帮助新药开发.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 病毒学 病毒学
- 结构生物学 结构生物学
背景情况:
- 乙型肝炎和甲型肝炎病毒 (HBV/HDV) 通过Na+-taurocholate共运输多 (NTCP) 受体感染肝细胞.
- 布列维 (BLV) 是一种经批准的药物,通过阻断preS1-NTCP相互作用来抑制HBV/HDV感染.
研究的目的:
- 阐明布莱维尔提德在NTCP上的抑制功能的结构基础.
- 要了解HBV/HDV入境抑制的机制由BLV.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定与BLV结合的人类NTCP的结构.
- 对BLV与NTCP域及其myristoyl组相互作用的结构分析.
主要成果:
- 冷EM结构显示,BLV有两个域:NTCP胆汁盐运输道中的插头和覆盖细胞外表面的字符串.
- BLV的N终端myristoyl组与NTCP的脂质暴露表面相互作用.
- 该结构解释了BLV抑制胆汁盐运输和病毒对接.
结论:
- BLV-NTCP结构提供了对HBV/HDV进入机制和宿主特异性的洞察.
- 这些结构信息可以指导针对HBV/HDV与NTCP对接的新型抑制剂的开发.
相关概念视频
Retrovirus Life Cycles
45.9K
Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
45.9K
Immune Response Against Viral Pathogens
780
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
780


