tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2022 Jul 19;119(29):e2205784119.
doi: 10.1073/pnas.2205784119. Epub 2022 Jun 29.
A broad and potent neutralization epitope in SARS-related coronaviruses
Meng Yuan[SUP] 1 [/SUP], Xueyong Zhu[SUP] 1 [/SUP], Wan-Ting He[SUP] 2 3 4 [/SUP], Panpan Zhou[SUP] 2 3 4 [/SUP], Chengzi I Kaku[SUP] 5 [/SUP], Tazio Capozzola[SUP] 2 [/SUP], Connie Y Zhu[SUP] 1 [/SUP], Xinye Yu[SUP] 1 [/SUP], Hejun Liu[SUP] 1 [/SUP], Wenli Yu[SUP] 1 [/SUP], Yuanzi Hua[SUP] 1 [/SUP], Henry Tien[SUP] 1 [/SUP], Linghang Peng[SUP] 2 [/SUP], Ge Song[SUP] 2 [/SUP], Christopher A Cottrell[SUP] 2 3 4 [/SUP], William R Schief[SUP] 2 3 4 6 [/SUP], David Nemazee[SUP] 2 [/SUP], Laura M Walker[SUP] 5 7 [/SUP], Raiees Andrabi[SUP] 2 3 4 [/SUP], Dennis R Burton[SUP] 2 3 4 6 [/SUP], Ian A Wilson[SUP] 1 3 4 8 [/SUP]
Affiliations
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.
Keywords: SARS-CoV-2; X-ray crystallography; conserved epitope; cross-neutralizing antibody; variants of concern.
. 2022 Jul 19;119(29):e2205784119.
doi: 10.1073/pnas.2205784119. Epub 2022 Jun 29.
A broad and potent neutralization epitope in SARS-related coronaviruses
Meng Yuan[SUP] 1 [/SUP], Xueyong Zhu[SUP] 1 [/SUP], Wan-Ting He[SUP] 2 3 4 [/SUP], Panpan Zhou[SUP] 2 3 4 [/SUP], Chengzi I Kaku[SUP] 5 [/SUP], Tazio Capozzola[SUP] 2 [/SUP], Connie Y Zhu[SUP] 1 [/SUP], Xinye Yu[SUP] 1 [/SUP], Hejun Liu[SUP] 1 [/SUP], Wenli Yu[SUP] 1 [/SUP], Yuanzi Hua[SUP] 1 [/SUP], Henry Tien[SUP] 1 [/SUP], Linghang Peng[SUP] 2 [/SUP], Ge Song[SUP] 2 [/SUP], Christopher A Cottrell[SUP] 2 3 4 [/SUP], William R Schief[SUP] 2 3 4 6 [/SUP], David Nemazee[SUP] 2 [/SUP], Laura M Walker[SUP] 5 7 [/SUP], Raiees Andrabi[SUP] 2 3 4 [/SUP], Dennis R Burton[SUP] 2 3 4 6 [/SUP], Ian A Wilson[SUP] 1 3 4 8 [/SUP]
Affiliations
- PMID: 35767670
- DOI: 10.1073/pnas.2205784119
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.
Keywords: SARS-CoV-2; X-ray crystallography; conserved epitope; cross-neutralizing antibody; variants of concern.