학술논문
A broad and potent neutralization epitope in SARS-related coronaviruses
Document Type
Report
Author
Yuan, Meng; Zhu, Xueyong; He, Wan-ting; Zhou, Panpan; Kaku, Chengzi I.; Capozzola, Tazio; Zhu, Connie Y.; Yu, Xinye; Liu, Hejun; Yu, Wenli; Hua, Yuanzi; Tien, Henry; Peng, Linghang; Song, Ge; Cottrell, Christopher A.; Schie, William R.; Nemazee, David; Walker, Laura M.; Andrabi, Raiees; Burton, Dennis R.; Wilson, Ian A.
Source
Proceedings of the National Academy of Sciences of the United States. July 19, 2022, Vol. 119 Issue 29, p1y, 8 p.
Subject
Language
English
ISSN
0027-8424
Abstract
Many neutralizing antibodies (nAbs) elicited to ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through natural infection and vaccination have reduced effectiveness to SARS-CoV-2 variants. Here, we show that therapeutic antibody ADG20 is able to neutralize SARS-CoV-2 variants of concern (VOCs) including Omicron (B.1.1.529) as well as other SARS-related coronaviruses. We delineate the structural basis of this relatively escape-resistant epitope that extends from one end of the receptor binding site (RBS) into the highly conserved CR3022 site. ADG20 can then benefit from high potency through direct competition with ACE2 in the more variable RBS and interaction with the more highly conserved CR3022 site. Importantly, antibodies that are able to target this site generally neutralize a broad range of VOCs, albeit with reduced potency against Omicron. Thus, this conserved and vulnerable site can be exploited for the design of universal vaccines and therapeutic antibodies. SARS-CoV-2 | variants of concern | cross-neutralizing antibody | conserved epitope | X-ray crystallography