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

Xiang-Yang Chi Renhong Yan Jun Zhang Guan-Ying Zhang Yuanyuan Zhang Meng Hao Zhe Zhang Pengfei Fan Yunzhu Dong Yilong Yang Zhengshan Chen Yingying Guo Jin-Long Zhang Yaning Li Xiaohong Song Yi Chen Lu Xia Ling Fu Lihua Hou Junjie Xu Changming Yu Jianmin Li Qiang Zhou Wei Chen

Published in: Science (New York, N.Y.) (2020)

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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