A Neutralizing Human Antibody Binds to the N-terminal Domain of the Spike Protein of SARS-CoV-2

Overview

Journal Science

Specialty Science

Date 2020 Jun 24

PMID 32571838

Citations 891

Authors

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

Affiliations

Soon will be listed here.

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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