An ultrapotent pan-β-coronavirus lineage B (β-CoV-B) neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope

• DOI: 10.1007/s13238-021-00871-6
• Publication Date: 2021-09-23T09:07:50Z
• Authors: Zezhong Liu; Wei Xu; Zhenguo Chen; Wangjun Fu; Wuqiang Zhan; Yidan Gao; Jie Zhou; Yunjiao Zhou; Jianbo Wu; Qian Wang; Xiang Zhang; Aihua Hao; Wei Wu; Qianqian Zhang; Yaming Li; Kaiyue Fan; Ruihong Chen; Qiaochu Jiang; Christian T Mayer; Till Schoofs; Youhua Xie; Shibo Jiang; Yumei Wen; Zhenghong Yuan; Kang Wang; Lu Lu; Lei Sun; Qiao Wang
• Keywords: Lineage (genetic); Coronavirus; 2019-20 coronavirus outbreak

Abstract New threats posed by the emerging circulating variants of SARS-CoV-2 highlight need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its variants, SARS-CoV bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels cross-reactivity induce antibody-dependent spike (S) protein-mediated cell-cell fusion, suggesting unique mode recognition XG014. Structural analyses reveal that recognizes epitope outside ACE2 site completely locks RBD in non-functional “down” conformation, while member XG005 directly competes position “up”. Single administration is effective protection against therapy infection vivo. Our findings suggest potential develop as pan-β-CoV-B therapeutics importance antigenic designing broadly protective vaccines β-CoV-B newly concern.