病毒中和抗体的高亲和度优化潜力与双胞胎氨酸稳定互补性决定区域3
Jing Li1, Dan-Dan Zeng2, Qi Yin1
1State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China.
Frontiers in cellular and infection microbiology
|January 30, 2026
概括
在中和单克隆抗体 (NMAbs) 中稳定H3 CDR区域显著增强人工智能 (AI) 优化,以改善SARS-CoV-2疗法. 这种结构性方法释放了对抗病毒进化的抗体开发的更大潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
- 病毒学 病毒学
背景情况:
- 中和单克隆抗体 (NMAbs) 对于对抗病毒进化至关重要.
- 重链互补性决定区域3 (H3 CDR) 的结构稳定性影响抗体亲和力成熟,但其在计算优化中的作用尚不清楚.
研究的目的:
- 调查H3 CDR形态稳定对SARS-CoV-2 NMAbs.AI驱动优化的影响.
- 评估优化抗体在体外和体内疗效.
主要方法:
- 一个人工智能 (AI) 模型被用来优化SARS-CoV-2 NMAbs的两个类别:一个具有稳定的H3 CDR (双氨酸基因图案),另一个具有灵活的H3 CDR循环.
- 在小鼠模型中,优化的抗体被评估为结合亲和力,伪病毒和活病毒中和,以及体内疗效.
- 结构分析阐明了与ACE2受体的相互作用.
主要成果:
- 通过双胞胎囊蛋白稳定H3 CDR显著改善了人工智能驱动的优化,从而提高了对SARS-CoV-2的结合亲和力和中和功效.
- 稳定组的优化抗体与ACE2受体的相互作用更紧密,与生物疗效相关.
- 在体内研究表明,在接受优化抗体治疗的小鼠中,有效抑制病毒复制并减少病毒载荷.
结论:
- 对H3CDR的 conformational稳定对于成功的AI驱动的NMAbs的亲和力成熟至关重要.
- 这项研究为抗体开发提供了战略框架,优先考虑结构稳定的H3 CDRs,以获得针对快速演变的病毒的强效治疗方法.
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