Human neutralizing antibodies elicited by SARS-CoV-2 infection
Human neutralizing antibodies elicited by SARS-CoV-2 infection
复制标题
SARS-CoV-2 感染引起的人类中和抗体
DOI：
10.1038/s41586-020-2380-z
复制
发表时间：
2020-05-26
期刊：
影响因子：
64.8
通讯作者：
Zhang, Linqi
中科院分区：
文献类型：
--
作者：
Ju, Bin;Zhang, Qi;Zhang, Linqi
由严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）引起的2019年冠状病毒病（COVID-19）大流行是一种全球卫生紧急情况，迫切需要干预（1-3）。SARS-CoV-2进入其靶细胞取决于病毒刺突蛋白的受体结合域（RBD）与其细胞受体血管紧张素转换酶2（ACE 2）之间的结合（2，4 -6）。在这里，我们报告了206个RBD特异性单克隆抗体的分离和鉴定，这些抗体来自8个SARS-CoV-2感染个体的单个B细胞。我们鉴定了有效中和SARS-CoV-2的抗体;这种活性与ACE 2竞争结合RBD相关。出乎意料的是，抗SARS-CoV-2抗体和感染的血浆不与SARS-CoV或中东呼吸综合征相关冠状病毒（MERS-CoV）的RBD交叉反应，尽管存在与其三聚体刺突蛋白的大量血浆交叉反应性。RBD结合抗体的晶体结构分析显示，空间位阻抑制病毒与ACE 2的结合，从而阻断病毒进入。这些发现表明，抗RBD抗体主要是病毒种属特异性抑制剂。在一项从SARS-CoV-2感染患者中分离的抗体的研究中，有效中和病毒的抗体与血管紧张素转换酶2竞争结合病毒刺突蛋白的受体结合域，这表明可以开发破坏这种相互作用的抗体来治疗SARS-CoV-2感染。
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a global health emergency that is in urgent need of intervention(1-3). The entry of SARS-CoV-2 into its target cells depends on binding between the receptor-binding domain (RBD) of the viral spike protein and its cellular receptor, angiotensin-converting enzyme 2 (ACE2)(2,4-6). Here we report the isolation and characterization of 206 RBD-specific monoclonal antibodies derived from single B cells from 8 individuals infected with SARS-CoV-2. We identified antibodies that potently neutralize SARS-CoV-2; this activity correlates with competition with ACE2 for binding to RBD. Unexpectedly, the anti-SARS-CoV-2 antibodies and the infected plasma did not cross-react with the RBDs of SARS-CoV or Middle East respiratory syndrome-related coronavirus (MERS-CoV), although there was substantial plasma cross-reactivity to their trimeric spike proteins. Analysis of the crystal structure of RBD-bound antibody revealed that steric hindrance inhibits viral engagement with ACE2, thereby blocking viral entry. These findings suggest that anti-RBD antibodies are largely viral-species-specific inhibitors. The antibodies identified here may be candidates for development of clinical interventions against SARS-CoV-2.In a study of antibodies isolated from patients infected with SARS-CoV-2, antibodies that potently neutralized the virus competed with angiotensin-converting enzyme 2 for binding to the receptor-binding domain of the viral spike protein, suggesting that antibodies that disrupt this interaction could be developed to treat SARS-CoV-2 infection.