将SARS-CoV-1中和抗体S230重新编程到SARS-CoV-2通过定向进化和基于分子对接的结合模式分析
Inji Jung1,2,3, Dinesh Kumar Sriramulu4, Sun-Gu Lee4
1Department of Biomedical Sciences, Graduate School, Korea University, Seoul 02707, Republic of Korea.
ACS synthetic biology
|November 14, 2025
概括
研究人员重新编程SARS-CoV-1抗体以使用定向进化和分子对接来准SARS-CoV-2. 修改后的抗体中和了SARS-CoV-2,证明了适应新兴病原体的抗体的新平台.
科学领域:
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
- 合成生物学 合成生物学
背景情况:
- 在SARS-CoV-1中和抗体S230缺乏针对SARS-CoV-2的活性.
- 开发广泛的中和抗体对于疫情准备至关重要.
研究的目的:
- 为了重新编程SARS-CoV-1抗体S230的抗原特异性,以准SARS-CoV-2.
- 为了研究抗体特异性重编程的分子基础.
主要方法:
- 从S230.0.中构建了一个易发生错误的单链可变片段 (scFv) 库.
- 使用细菌显示器对SARS-CoV-2受体结合域 (RBD) 进行了扫描.
- 利用分子对接和逆转分析来理解突变效应.
主要成果:
- 鉴定了IJ36-V,一种优化的抗体变体,具有高效的SARS-CoV-2中和.
- IJ36-V保留了与SARS-CoV-1 RBD的交叉反应,显示了扩展的功能宽度.
- 发现两种特定突变 (R56W和N57Y) 能够协同稳定结合界面.
结论:
- 一个有限的协同突变组可以使相关但不同的标的抗原识别成为可能.
- 使用合成生物学建立了一个模块化和可进化的抗体重编程平台.
- 抗体支架对新出现的病毒威胁的快速适应.
相关概念视频
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