期刊
SCIENCE
卷 369, 期 6504, 页码 650-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abc6952
关键词
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资金
- National Key R&D Program of China [2020YFC0841400]
- National Natural Science Foundation of China [31971123, 81803429, 81703048, 31900671, 81920108015, 31930059]
- Key R&D Program of Zhejiang Province [2020C04001]
- SARS-CoV-2 emergency project of the Science and Technology Department of Zhejiang Province [2020C03129]
- Leading Innovative and Entrepreneur Team Introduction Program of Hangzhou
- National Science and Technology Major Project of the Ministry of Science and Technology of China [2018ZX10101003-005-007]
- Special Research Program of Novel Coronavirus Pneumonia of Westlake University
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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