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通过强大的治疗抗体中和SARS-CoV-2的结构基础

Zhe Lv^1,2, Yong-Qiang Deng³, Qing Ye³

¹CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.

Science (New York, N.Y.)

|July 25, 2020

概括

一种新的人性化单克隆抗体H014通过向尖端蛋白有效中和SARS-CoV-2. 在COVID-19小鼠模型中,这种抗体降低了病毒载量并防止了肺损伤,显示出治疗潜力.

科学领域:

免疫学和病毒学
结构生物学
治疗发展

背景情况:

由SARS-CoV-2引起的COVID-19大流行是一个重大的全球健康挑战.
目前还没有专门用于治疗COVID-19的批准疫苗或治疗方法.

研究的目的:

识别和表征一种具有强大中和作用的新型人性化单克隆抗体,用于对抗SARS-CoV-2.
调查抗体的作用机制和结构基础.
在相关的临床前模型中评估抗体的治疗潜力.

主要方法:

使用SARS-CoV-2和SARS-CoV伪病毒和真实SARS-CoV-2进行中和测试.
在人体血管激素转化酶2 (ACE2) 鼠标模型中的体内研究.
电子显微镜 (Cryo-EM) 用于结构特征.
生物化学,细胞和病毒学分析以阐明作用机制.

主要成果:

人性化的单克隆抗体H014在纳米度下有效中和SARS-CoV-2.
H014针对SARS-CoV-2尖端 (S) 蛋白的受体结合域 (RBD).
在ACE2小鼠模型中,使用H014降低了感染肺部的病毒标位,并预防了肺病变.
低温EM检测显示H014结合于RBD的前所未有的形状表位.
H014被证明可以抑制SARS-CoV-2与宿主细胞的附着.

结论:

H014是一种强有力的中和抗体,可用于治疗SARS-CoV-2.
抗体的机制包括通过向特定的形状表位来阻止病毒的附着.
基于抗体的干预措施是治疗COVID-19的关键策略.

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