E484Q和L452R突变对SARS-CoV-2的结构和结合行为的影响 B.1.617.1使用深度学习AlphaFold2,分子对接和动力学模拟
Yanqi Jiao1, Yichen Xing1, Yao Sun1
1School of Science, Harbin Institute of Technology (Shenzhen), Shenzhen 518055, China.
International journal of molecular sciences
|July 29, 2023
概括
在SARS-CoV-2 B.1.617.1中的L452R和E484Q突变降低了对HACE2和单克隆抗体的结合亲和力,这表明免疫规避. 这项研究提供了对变体感染性和抗体有效性的计算见解.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 计算生物学 计算生物学
背景情况:
- 包括B.1.617.1在内的SARS-CoV-2变种具有影响病毒结合和免疫逃避的突变.
- 像L452R和E484Q这样的特定突变引起了人们对抗体逃避增加的担忧.
研究的目的:
- 调查B.1.617.1尖端蛋白中的L452R和E484Q突变的结构和结合影响.
- 评估这些突变对与人类血管酶转化酶2 (hACE2) 和中和抗体的相互作用的影响.
主要方法:
- 利用深度学习 (AlphaFold2) 进行S蛋白结构预测和验证.
- 采用分子对接和分子动力学模拟来分析结合亲和和稳定性.
- 评估了与 hACE2 和三种已批准的中和单克隆抗体 (mAbs) 的相互作用.
主要成果:
- L452R和E484Q双基因突变减少了键,并增加了与HACE2的相互作用能量,表明稳定性和结合亲和力降低.
- 尽管对接得分有利,但分子动力学显示,随着时间的推移,结合亲和力会变得更差.
- 双重突变变体对中和mAbs的结合亲和力降低,这意味着中和效率较低.
结论:
- 在SARS-CoV-2 B.1.617.1中的L452R和E484Q突变通过降低对 hACE2的结合亲和力和中和抗体,有助于免疫逃避.
- 这项研究的计算见解可以指导未来对SARS-CoV-2变种和抗体开发的研究.
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