结构功能分析揭示了HIV-1 CRF01_AE对进入抑制剂泰姆萨维尔耐药性的关键分子决定因素
Jérémie Prévost1,2, Yaozong Chen3, Fei Zhou4
1Centre de Recherche du CHUM, Montreal, QC, Canada.
Nature communications
|October 23, 2023
概括
艾滋病毒-1 病毒中的坦萨维尔耐药性涉及不止一个突变. 在gp120内域中的多个残留物有助于耐药性,而不仅仅是主要突变部位.
科学领域:
- 病毒学 病毒学
- 药物耐药性机制 药物耐药性机制
- 结构生物学 结构生物学
背景情况:
- 姆萨维尔是一种HIV-1进入抑制剂,向CD4 (分化集群4) 和信封糖蛋白 (Env) 之间的相互作用.
- 已知Temsavir的疗效受到Env中的特定残留物的影响,特别是在375位.
研究的目的:
- 阐明艾滋病毒-1的马维尔耐药性背后的详细机制.
- 为了识别除了位置375之外的其他因素,这些因素有助于特姆萨维尔耐药性.
主要方法:
- 使用工程HIV-1病毒进行结构功能分析.
- 分析可溶性gp120的三分剂变体.
- 研究药物结合相互作用和形状变化.
主要成果:
- 艾滋病毒-1对姆萨维尔的耐药性不仅仅是由Env.中的375残留物决定的.
- 在gp120内域中至少有六种额外的残留物有助于抵抗,其中一些远离药物结合部位.
- 抵抗源于His375与其他内部域残留物之间的交叉声响,从而影响Env的构造.
结论:
- 姆萨维尔耐药性是一种复杂的现象,涉及HIV-1包膜糖蛋白中的多个残留物.
- 药物适应其结合方式以适应Env的结构变化的能力可能有助于其广泛的抗病毒活性.
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