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科学家发现有效中和SARS-CoV-2 和SARS-CoV的治疗性抗体
作者:小柯机器人 发布时间:2020/7/24 20:08:41

近日,中国科学院生物物理研究所研究人员合作发现有效中和SARS-CoV-2 和SARS-CoV的治疗性抗体。相关论文于2020年7月23日在线发表在《科学》杂志上。

研究人员报道了一种人源化单克隆抗体H014,其通过与S受体结合域(RBD)结合,可有效中和SARS-CoV-2和SARS-CoV伪病毒以及真正的SARS-CoV-2。重要的是,在hACE2小鼠模型中,H014的给药可降低感染肺部的SARS-CoV-2滴度,并预防肺部病理。与H014 Fab片段复合的SARS-CoV-2 S三聚体的冷冻电镜表征揭示了一种新颖的构象表位,仅当RBD处于开放构象时才可结合。
 
生化、细胞、病毒学和结构研究表明,H014阻止SARS-CoV-2附着于其宿主细胞受体。靶向SARS-CoV和SARS-CoV-2的中和抗体表位分析揭示了广泛的交叉保护性表位。这些结果突出了抗体的治疗性干预措施在COVID-19治疗中的关键作用。
 
附:英文原文

Title: Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody

Author: Zhe Lv, Yong-Qiang Deng, Qing Ye, Lei Cao, Chun-Yun Sun, Changfa Fan, Weijin Huang, Shihui Sun, Yao Sun, Ling Zhu, Qi Chen, Nan Wang, Jianhui Nie, Zhen Cui, Dandan Zhu, Neil Shaw, Xiao-Feng Li, Qianqian Li, Liangzhi Xie, Youchun Wang, Zihe Rao, Cheng-Feng Qin, Xiangxi Wang

Issue&Volume: 2020/07/23

Abstract: Abstract The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we reported a humanized monoclonal antibody, H014, efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nM level by engaging the S receptor binding domain (RBD). Importantly, H014 administration reduced SARS-CoV-2 titers in the infected lungs and prevented pulmonary pathology in hACE2 mouse model. Cryo-EM characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a novel conformational epitope, which is only accessible when the RBD is in open conformation. Biochemical, cellular, virological and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncover broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19.

DOI: 10.1126/science.abc5881

Source: https://science.sciencemag.org/content/early/2020/07/22/science.abc5881

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037