通过人类单克隆SARS-CoV抗体对SARS-CoV-2进行交叉中和
Dora Pinto1, Young-Jun Park2, Martina Beltramello1
1Humabs BioMed SA, Vir Biotechnology, Bellinzona, Switzerland.
Nature
|May 19, 2020
概括
在一名SARS-CoV幸存者身上发现了一种强大的中和抗体S309. 这种抗体有效地向SARS-CoV-2尖端糖蛋白,为COVID-19 (冠状病毒疾病2019) 的治疗和预防提供了潜在的可能性.
科学领域:
- 病毒学
- 免疫学
- 结构生物学
背景情况:
- 由SARS-CoV-2引起的持续的COVID-19大流行需要紧急开发疫苗和治疗方法.
- 由于其在宿主细胞进入中的作用,SARS-CoV-2尖端 (S) 糖蛋白是中和抗体的关键目标.
- 以往与SARS-CoV (严重急性呼吸道综合征冠状病毒) 的经验为了解交叉反应性免疫提供了基础.
研究的目的:
- 识别和描述针对SARS-CoV-2的强效中和单克隆抗体.
- 研究有前途的抗体候选者的作用机制和表位识别.
- 探索抗体尾酒的潜力,
主要方法:
- 从有SARS-CoV感染史的个体中分离出记忆B细胞.
- 针对SARS-CoV-2尖端糖蛋白的单克隆抗体的查和特征.
- 伪病毒和真实的病毒中和试验.
- 低温电子显微镜和结合测试以确定表位和与受体结合域的相互作用.
主要成果:
- 鉴定了S309,一种对SARS-CoV-2和SARS-CoV有效的强效中和抗体.
- S309与S糖蛋白的受体结合域结合,识别了Sarbecovirus亚系中的一个保存的糖表位.
- S309与宿主细胞受体的附着不竞争.
- 包括S309在内的抗体合剂表现出增强的中和和限制病毒逃逸的潜力.
结论:
- S309是一种有前途的COVID-19治疗候选物,针对SARS-CoV-2尖端蛋白的保存表位.
- 抗体尾酒提供了一种提高中和效率和克服病毒抗性的策略.
- 这些发现支持开发基于S309的预防和治疗SARS-CoV-2感染的疗法.
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