A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2
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Open Access
- 7 August 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 369 (6504), 650-655
- https://doi.org/10.1126/science.abc6952
Abstract
Developing therapeutics against 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 ten convalescent COVID-19 patients. Three mAbs showed neutralizing activities against authentic SARS-CoV-2. An 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 its cryo-EM structure in complex with the S protein to an overall resolution of 3.1 Angstrom and local resolution of 3.3 Angstrom for the 4A8-NTD interface. This points to the NTD as a promising target for therapeutic mAbs against COVID-19.Keywords
Funding Information
- National Natural Science Foundation of China (31971123)
- National Natural Science Foundation of China (81803429)
- National Natural Science Foundation of China (81703048)
- National Natural Science Foundation of China (31900671)
- National Natural Science Foundation of China (81920108015)
- National Natural Science Foundation of China (31930059)
- Key RD 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
- Special Research Program of Novel Coronavirus Pneumonia of Westlake University
- National Key Research and Development Program of China Stem Cell and Translational Research (2020YFC0841400)
- National Science and Technology Major Project of the Ministry of Science and Technology of China (2018ZX10101003-005-007)
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