tetano
Editor, Senior Moderator
Nat Commun
. 2025 Aug 15;16(1):7580.
doi: 10.1038/s41467-025-63101-1. A broadly neutralizing antibody recognizes a unique epitope with a signature motif common across coronaviruses
Lei Yan[SUP] 1 [/SUP], Fulian Wang[SUP] 1 [/SUP], Michelle Hill[SUP] 2 [/SUP], Juliane Brun[SUP] 3 [/SUP], Ze Liang[SUP] 4 [/SUP], Xinyu Shi[SUP] 4 [/SUP], Liangminghui Zhang[SUP] 4 [/SUP], Xiuxiu He[SUP] 4 [/SUP], Yu Li[SUP] 1 [/SUP], Qianping Huang[SUP] 1 [/SUP], Xuxue Dong[SUP] 1 [/SUP], Huanzhen Liu[SUP] 1 [/SUP], Yi Zhang[SUP] 1 [/SUP], Lili Liu[SUP] 1 [/SUP], Raymond A Dwek[SUP] 3 [/SUP], Nicole Zitzmann[SUP] 3 [/SUP], Aibin Liang[SUP] 5 [/SUP], Guang Yang[SUP] 6 7 8 [/SUP]
Affiliations
Cross-reactive antibodies targeting multiple epitopes have been identified in Sarbecoviruses, but the precise molecular mechanism(s) behind the crossreactivity remain poorly understood. Here, we isolate 3D1, a broadly neutralizing antibody (bnAb) derived from a human combinatorial antibody library targeting the conserved HR1 domain. 3D1 uniquely recognizes a β-turn fold comprising a 6-mer peptide (pep[SUP]DVVNQN/Q[/SUP]) that forms during a pre-hairpin transition state, occurring exclusively before membrane fusion during viral infection. 3D1 effectively neutralizes a wide range of live SARS-CoV-2 wild-type strains except for Omicron, which evades neutralization due to a detrimental point mutation (Q954H). Notably, this cryptic epitope reveals a signature motif that extends throughout the core region of coronaviruses and is also present in various RNA viruses, including HIV and Marburgvirus. 3D1 functions as a natural or background antibody capable of binding to a diverse array of non-self antigens. 3D1's cross-reactivity underscores the effectiveness of the library approach, which encompasses the entire antibody repertoire.
. 2025 Aug 15;16(1):7580.
doi: 10.1038/s41467-025-63101-1. A broadly neutralizing antibody recognizes a unique epitope with a signature motif common across coronaviruses
Lei Yan[SUP] 1 [/SUP], Fulian Wang[SUP] 1 [/SUP], Michelle Hill[SUP] 2 [/SUP], Juliane Brun[SUP] 3 [/SUP], Ze Liang[SUP] 4 [/SUP], Xinyu Shi[SUP] 4 [/SUP], Liangminghui Zhang[SUP] 4 [/SUP], Xiuxiu He[SUP] 4 [/SUP], Yu Li[SUP] 1 [/SUP], Qianping Huang[SUP] 1 [/SUP], Xuxue Dong[SUP] 1 [/SUP], Huanzhen Liu[SUP] 1 [/SUP], Yi Zhang[SUP] 1 [/SUP], Lili Liu[SUP] 1 [/SUP], Raymond A Dwek[SUP] 3 [/SUP], Nicole Zitzmann[SUP] 3 [/SUP], Aibin Liang[SUP] 5 [/SUP], Guang Yang[SUP] 6 7 8 [/SUP]
Affiliations
- PMID: 40813592
- PMCID: PMC12354777
- DOI: 10.1038/s41467-025-63101-1
Cross-reactive antibodies targeting multiple epitopes have been identified in Sarbecoviruses, but the precise molecular mechanism(s) behind the crossreactivity remain poorly understood. Here, we isolate 3D1, a broadly neutralizing antibody (bnAb) derived from a human combinatorial antibody library targeting the conserved HR1 domain. 3D1 uniquely recognizes a β-turn fold comprising a 6-mer peptide (pep[SUP]DVVNQN/Q[/SUP]) that forms during a pre-hairpin transition state, occurring exclusively before membrane fusion during viral infection. 3D1 effectively neutralizes a wide range of live SARS-CoV-2 wild-type strains except for Omicron, which evades neutralization due to a detrimental point mutation (Q954H). Notably, this cryptic epitope reveals a signature motif that extends throughout the core region of coronaviruses and is also present in various RNA viruses, including HIV and Marburgvirus. 3D1 functions as a natural or background antibody capable of binding to a diverse array of non-self antigens. 3D1's cross-reactivity underscores the effectiveness of the library approach, which encompasses the entire antibody repertoire.