受到约束的进化道塑造了病毒免疫逃生之道
Marian Huot1,2, Dianzhuo Wang2,3, Eugene Shakhnovich2
1Laboratory of Physics of the École Normale Supérieure, CNRS UMR 8023 and PSL Research, Sorbonne Université, 24 rue Lhomond, Paris, France.
bioRxiv : the preprint server for biology
|November 24, 2025
概括
预测病毒从抗体中逃脱是理解变体演变的关键. 一个新的框架显示,由于蛋白质结构和抗体限制,免疫逃避遵循有限的,可行的途径,减缓了适应.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 进化生物学 进化生物学
背景情况:
- 在免疫压力下的病毒进化推动了抗体耐药变体的出现.
- 了解病毒适应的限制对于预测未来疫情至关重要.
研究的目的:
- 开发一种概率框架,用于在免疫压力下预测病毒进化轨迹.
- 确定影响病毒适应途径的关键约束因素 (蛋白质活力和抗体逃逸).
主要方法:
- 利用在结构同类和深度突变扫描数据上训练的生成模型.
- 开发了一个平均场近似来分析进化路径合集.
- 将框架应用于SARS-CoV-2受体结合域.
主要成果:
- 免疫逃避是通过有限数量的可行的进化途径进行的.
- 该框架准确地预测了SARS-CoV-2变种的突变部位.
- 抗体组合与脱相关的逃生形状显著减缓病毒适应.
结论:
- 病毒适应受到蛋白质结构活力和抗体逃生机制的限制.
- 进化轨迹的预测建模可以预测变种的出现.
- 战略性抗体尾酒设计可以增强对病毒演变的治疗疗效.
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