A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2

被引：1100

作者：

Chi, Xiangyang ^{[1
]}

Yan, Renhong ^{[2
]}

Zhang, Jun ^{[1
]}

Zhang, Guanying ^{[1
]}

Zhang, Yuanyuan ^{[2
]}

Hao, Meng ^{[1
]}

Zhang, Zhe ^{[1
]}

Fan, Pengfei ^{[1
]}

Dong, Yunzhu ^{[1
]}

Yang, Yilong ^{[1
]}

Chen, Zhengshan ^{[1
]}

Guo, Yingying ^{[2
]}

Zhang, Jinlong ^{[1
]}

Li, Yaning ^{[3
]}

Song, Xiaohong ^{[1
]}

Chen, Yi ^{[1
]}

Xia, Lu ^{[2
]}

Fu, Ling ^{[1
]}

Hou, Lihua ^{[1
]}

Xu, Junjie ^{[1
]}

Yu, Changming ^{[1
]}

Li, Jianmin ^{[1
]}

Zhou, Qiang ^{[2
]}

Chen, Wei ^{[1
]}

机构：

[1] Acad Mil Med Sci AMMS, Beijing Inst Biotechnol, Beijing 100071, Peoples R China

[2] Westlake Univ, Sch Life Sci, Westlake Inst Adv Study, Inst Biol,Key Lab Struct Biol Zhejiang Prov, Hangzhou 310024, Zhejiang, Peoples R China

[3] Tsinghua Univ, Beijing Adv Innovat Ctr Struct Biol, Tsinghua Peking Joint Ctr Life Sci, Sch Life Sci, Beijing 100084, Peoples R China

来源：

SCIENCE | 2020年 / 369卷 / 6504期

基金：

中国国家自然科学基金;

关键词：

CRYO-EM STRUCTURE; FUNCTIONAL RECEPTOR; CORONAVIRUS; ENTRY; ACE2; PHYLOGENIES; ACTIVATION; VACCINES; FEATURES; ACID;

D O I：

10.1126/science.abc6952

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Developing therapeutics against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be guided by the distribution of epitopes, not only on the receptor binding domain (RBD) of the Spike (S) protein but also across the full Spike (S) protein. We isolated and characterized monoclonal antibodies (mAbs) from 10 convalescent COVID-19 patients. Three mAbs showed neutralizing activities against authentic SARS-CoV-2. One mAb, named 4A8, exhibits high neutralization potency against both authentic and pseudotyped SARS-CoV-2 but does not bind the RBD. We defined the epitope of 4A8 as the N-terminal domain (NTD) of the S protein by determining with cryo-eletron microscopy its structure in complex with the S protein to an overall resolution of 3.1 angstroms and local resolution of 3.3 angstroms for the 4A8-NTD interface. This points to the NTD as a promising target for therapeutic mAbs against COVID-19.

引用

页码：650 / +

页数：49

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