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SARS-CoV-2受体结合域的抗原解剖学
Wanwisa Dejnirattisai1, Daming Zhou2, Helen M Ginn3
1Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
Cell
|March 23, 2021
概括
研究人员确定了针对SARS-CoV-2的377种人类单克隆抗体 (mAbs). 高效的中和抗体主要阻断病毒的进入,其中一些在动物模型中表现出保护作用.
科学领域:
- 免疫学
- 病毒学
- 结构生物学
背景情况:
- 抗体对抗SARS-CoV-2的免疫防御至关重要.
- 单克隆抗体 (mAbs) 正在作为治疗药物进行研究.
- 了解抗体与SARS-CoV-2尖端蛋白结合是非常重要的.
研究的目的:
- 识别和描述针对SARS-CoV-2尖端蛋白的人类单克隆抗体,特别是受体结合域 (RBD).
- 在RBD上绘制抗体结合部位并分析中和的结构基础.
- 在临床前模型中评估强效中和抗体的保护效果.
主要方法:
- 对377种人类单克隆抗体针对SARS-CoV-2尖端蛋白的鉴定和查.
- 开发一种以竞争数据为导向的方法来绘制RBD绑定站点.
- 使用X射线结晶学和冷电子显微镜对19个Fab抗原复合物的结构分析.
主要成果:
- 鉴定了80种与RBD结合的抗体,其中高度中和的mAbs具有聚焦结合位.
- 确定最强的中和 mAbs 阻断病毒受体相互作用,其中一个针对独特的 N-终端域表位.
- 结构分析揭示了强效中和抗体的新结合方式.
结论:
- 针对SARS-CoV-2的高效中和单克隆抗体主要针对RBD并阻止病毒的进入.
- 许多有力的中和抗体利用常见的V基因,并且接近胚胎线,这表明它们具有广泛适用性的潜力.
- 强烈中和的mAbs在动物模型中表现出预防性和治疗性保护,支持其治疗潜力.
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