Human neutralizing antibodies elicited by SARS-CoV-2 infection

作者：Ju, Bin; Zhang, Qi; Ge, Jiwan; Wang, Ruoke; Sun, Jing; Ge, Xiangyang; Yu, Jiazhen; Shan, Sisi; Zhou, Bing; Song, Shuo; Tang, Xian; Yu, Jinfang; Lan, Jun; Yuan, Jing; Wang, Haiyan; Zhao, Juanjuan; Zhang, Shuye; Wang, Youchun; Shi, Xuanling; Liu, Lei; Zhao, Jincun; Wang, Xinquan^*; Zhang, Zheng^*; Zhang, Linqi^*

来源：Nature, 2020, 584(7819): 115-+.

DOI：10.1038/s41586-020-2380-z

• SARS CORONAVIRUS
• SPIKE PROTEIN
• COV
• VACCINE
• BINDING

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.

• 单位
  复旦大学; 广州医学院; 清华大学; 1