结构上解决的SARS-CoV-2抗体在严重感染的仓鼠中显示出高效率,并提供强大的尾酒配对策略
Shuo Du1, Yunlong Cao2, Qinyu Zhu1
1School of Life Sciences, Peking University, Beijing 100871, China.
Cell
|September 24, 2020
概括
一种新的中和抗体BD-368-2通过结合所有受体结合域来阻止SARS-CoV-2的进入. 这种抗体具有治疗潜力,有效治疗子的COVID-19并增强其他抗体治疗方法.
科学领域:
- 病毒学
- 免疫学
- 结构生物学
背景情况:
- 了解SARS-CoV-2中和机制对于开发有效的COVID-19疗法至关重要.
- 之前已经发现了强效的中和抗体BD-368-2,但其作用机制尚不清楚.
研究的目的:
- 阐明SARS-CoV-2中和抗体BD-368-2的中和机制.
- 评估BD-368-2在临床前模型中的疗效及其组合治疗的潜力.
主要方法:
- 在3.5 Å分辨率下确定了BD-368-2/trimeric-spike复合物的冷电子显微镜 (冷EM) 结构.
- 评估了BD-368-2在感染SARS-CoV-2的成年仓鼠中的体内治疗效果.
- 通过具有受体结合域 (RBD) 的三元共晶结构研究了BD-368-2的表位.
主要成果:
- 不管RBD的形状如何,BD-368-2同时占据了所有三个RBD,完全阻断了ACE2受体的结合.
- 在低剂量和不同时间给药时,BD- 368-2 证明了对子的治疗效果,预防严重的间歇性肺炎.
- BD-368-2的表位与常见的复发性中和抗体结合部位不同,允许与其他抗体结合时进行协同中和.
- 用BD-368-2和复发性中和抗体进行的组合治疗实现了伪病毒的皮科莫尔中和,并克服了中和脱离突变.
结论:
- BD-368-2 采用了广泛的 RBD 阻断的新型机制,用于有效的 SARS-CoV-2 中和.
- 作为单一疗法和组合疗法,BD-368-2对COVID-19治疗具有显著的治疗潜力.
- 已识别的表位为开发下一代SARS-CoV-2疗法提供了一个新的目标,该疗法能够逃避现有的耐药性突变.
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