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A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2.
Science. 2020 08 07; 369(6504):650-655.Sci

Abstract

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.

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ncbi.nlm.nih.gov
sciencemag.org
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Authors+Show Affiliations

Chi X
Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
Yan R
Key Laboratory of Structural Biology of Zhejiang Province, Institute of Biology, Westlake Institute for Advanced Study, School of Life Sciences, Westlake University, Hangzhou 310024, Zhejiang Province, China.
Zhang J
Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
Zhang G
Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
Zhang Y
Key Laboratory of Structural Biology of Zhejiang Province, Institute of Biology, Westlake Institute for Advanced Study, School of Life Sciences, Westlake University, Hangzhou 310024, Zhejiang Province, China.
Hao M
Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
Zhang Z
Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
Fan P
Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
Dong Y
Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
Yang Y
Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
Chen Z
Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
Guo Y
Key Laboratory of Structural Biology of Zhejiang Province, Institute of Biology, Westlake Institute for Advanced Study, School of Life Sciences, Westlake University, Hangzhou 310024, Zhejiang Province, China.
Zhang J
Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
Li Y
Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Song X
Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
Chen Y
Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
Xia L
Key Laboratory of Structural Biology of Zhejiang Province, Institute of Biology, Westlake Institute for Advanced Study, School of Life Sciences, Westlake University, Hangzhou 310024, Zhejiang Province, China.
Fu L
Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
Hou L
Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
Xu J
Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
Yu C
Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China.
Li J
Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China. cw0226@foxmail.com zhouqiang@westlake.edu.cn lijmqz@126.com.
Zhou Q
Key Laboratory of Structural Biology of Zhejiang Province, Institute of Biology, Westlake Institute for Advanced Study, School of Life Sciences, Westlake University, Hangzhou 310024, Zhejiang Province, China. cw0226@foxmail.com zhouqiang@westlake.edu.cn lijmqz@126.com.
Chen W
Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China. cw0226@foxmail.com zhouqiang@westlake.edu.cn lijmqz@126.com.

MeSH

AdultAngiotensin-Converting Enzyme 2AnimalsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralAntibody AffinityAntibody SpecificityAntigens, ViralB-LymphocytesBetacoronavirusCOVID-19Chlorocebus aethiopsCoronavirus InfectionsCoronavirus Nucleocapsid ProteinsCryoelectron MicroscopyEnzyme-Linked Immunosorbent AssayGenes, Immunoglobulin Heavy ChainHumansImmunologic MemoryMiddle AgedMutationNucleocapsid ProteinsPandemicsPeptidyl-Dipeptidase APhosphoproteinsPneumonia, ViralProtein DomainsProtein Interaction Domains and MotifsReceptors, CoronavirusReceptors, VirusSARS-CoV-2Spike Glycoprotein, CoronavirusVero CellsYoung Adult

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32571838

Citation

Chi, Xiangyang, et al. "A Neutralizing Human Antibody Binds to the N-terminal Domain of the Spike Protein of SARS-CoV-2." Science (New York, N.Y.), vol. 369, no. 6504, 2020, pp. 650-655.
Chi X, Yan R, Zhang J, et al. A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2. Science. 2020;369(6504):650-655.
Chi, X., Yan, R., Zhang, J., Zhang, G., Zhang, Y., Hao, M., Zhang, Z., Fan, P., Dong, Y., Yang, Y., Chen, Z., Guo, Y., Zhang, J., Li, Y., Song, X., Chen, Y., Xia, L., Fu, L., Hou, L., ... Chen, W. (2020). A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2. Science (New York, N.Y.), 369(6504), 650-655. https://doi.org/10.1126/science.abc6952
Chi X, et al. A Neutralizing Human Antibody Binds to the N-terminal Domain of the Spike Protein of SARS-CoV-2. Science. 2020 08 7;369(6504):650-655. PubMed PMID: 32571838.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2. AU - Chi,Xiangyang, AU - Yan,Renhong, AU - Zhang,Jun, AU - Zhang,Guanying, AU - Zhang,Yuanyuan, AU - Hao,Meng, AU - Zhang,Zhe, AU - Fan,Pengfei, AU - Dong,Yunzhu, AU - Yang,Yilong, AU - Chen,Zhengshan, AU - Guo,Yingying, AU - Zhang,Jinlong, AU - Li,Yaning, AU - Song,Xiaohong, AU - Chen,Yi, AU - Xia,Lu, AU - Fu,Ling, AU - Hou,Lihua, AU - Xu,Junjie, AU - Yu,Changming, AU - Li,Jianmin, AU - Zhou,Qiang, AU - Chen,Wei, Y1 - 2020/06/22/ PY - 2020/05/08/received PY - 2020/06/17/accepted PY - 2020/6/24/pubmed PY - 2020/8/25/medline PY - 2020/6/24/entrez SP - 650 EP - 655 JF - Science (New York, N.Y.) JO - Science VL - 369 IS - 6504 N2 - 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. SN - 1095-9203 UR - https://www.unboundmedicine.com/medline/citation/32571838/A_neutralizing_human_antibody_binds_to_the_N_terminal_domain_of_the_Spike_protein_of_SARS_CoV_2_ L2 - https://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=32571838 DB - PRIME DP - Unbound Medicine ER -