Author: Xiangyang Chi, Renhong Yan, Jun Zhang, Guanying Zhang, Yuanyuan Zhang, Meng Hao, Zhe Zhang, Pengfei Fan, Yunzhu Dong, Yilong Yang, Zhengshan Chen, Yingying Guo, Jinlong Zhang, Yaning Li, Xiaohong Song, Yi Chen, Lu Xia, Ling Fu, Lihua Hou, Junjie Xu, Changming Yu, Jianmin Li, Qiang Zhou, Wei Chen
Abstract: 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.