A broadly neutralizing antibody recognizes a unique epitope with a signature motif common across coronaviruses
Abstract 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...
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-63101-1 |
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| author | Lei Yan Fulian Wang Michelle Hill Juliane Brun Ze Liang Xinyu Shi Liangminghui Zhang Xiuxiu He Yu Li Qianping Huang Xuxue Dong Huanzhen Liu Yi Zhang Lili Liu Raymond A. Dwek Nicole Zitzmann Aibin Liang Guang Yang |
| author_facet | Lei Yan Fulian Wang Michelle Hill Juliane Brun Ze Liang Xinyu Shi Liangminghui Zhang Xiuxiu He Yu Li Qianping Huang Xuxue Dong Huanzhen Liu Yi Zhang Lili Liu Raymond A. Dwek Nicole Zitzmann Aibin Liang Guang Yang |
| author_sort | Lei Yan |
| collection | DOAJ |
| description | Abstract 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 (pepDVVNQN/Q) 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. |
| format | Article |
| id | doaj-art-98a0b1a3f29f472196cab91201c93bbb |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-98a0b1a3f29f472196cab91201c93bbb2025-08-20T03:43:16ZengNature PortfolioNature Communications2041-17232025-08-0116111410.1038/s41467-025-63101-1A broadly neutralizing antibody recognizes a unique epitope with a signature motif common across coronavirusesLei Yan0Fulian Wang1Michelle Hill2Juliane Brun3Ze Liang4Xinyu Shi5Liangminghui Zhang6Xiuxiu He7Yu Li8Qianping Huang9Xuxue Dong10Huanzhen Liu11Yi Zhang12Lili Liu13Raymond A. Dwek14Nicole Zitzmann15Aibin Liang16Guang Yang17Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech UniversityShanghai Institute for Advanced Immunochemical Studies, ShanghaiTech UniversityJames & Lillian Martin Centre, Sir William Dunn School of Pathology, University of OxfordDepartment of Biochemistry, Oxford Glycobiology InstituteInternational Research Center of Synthetic Biology, School of Food Science and Pharmaceutical Engineering, Nanjing Normal UniversityInternational Research Center of Synthetic Biology, School of Food Science and Pharmaceutical Engineering, Nanjing Normal UniversityInternational Research Center of Synthetic Biology, School of Food Science and Pharmaceutical Engineering, Nanjing Normal UniversityInternational Research Center of Synthetic Biology, School of Food Science and Pharmaceutical Engineering, Nanjing Normal UniversityShanghai Institute for Advanced Immunochemical Studies, ShanghaiTech UniversityShanghai Institute for Advanced Immunochemical Studies, ShanghaiTech UniversityShanghai Institute for Advanced Immunochemical Studies, ShanghaiTech UniversityShanghai Institute for Advanced Immunochemical Studies, ShanghaiTech UniversityShanghai Institute for Advanced Immunochemical Studies, ShanghaiTech UniversityShanghai Institute for Advanced Immunochemical Studies, ShanghaiTech UniversityDepartment of Biochemistry, Oxford Glycobiology InstituteDepartment of Biochemistry, Oxford Glycobiology InstituteDepartment of Hematology, Tongji Hospital, Tongji University School of MedicineShanghai Institute for Advanced Immunochemical Studies, ShanghaiTech UniversityAbstract 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 (pepDVVNQN/Q) 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.https://doi.org/10.1038/s41467-025-63101-1 |
| spellingShingle | Lei Yan Fulian Wang Michelle Hill Juliane Brun Ze Liang Xinyu Shi Liangminghui Zhang Xiuxiu He Yu Li Qianping Huang Xuxue Dong Huanzhen Liu Yi Zhang Lili Liu Raymond A. Dwek Nicole Zitzmann Aibin Liang Guang Yang A broadly neutralizing antibody recognizes a unique epitope with a signature motif common across coronaviruses Nature Communications |
| title | A broadly neutralizing antibody recognizes a unique epitope with a signature motif common across coronaviruses |
| title_full | A broadly neutralizing antibody recognizes a unique epitope with a signature motif common across coronaviruses |
| title_fullStr | A broadly neutralizing antibody recognizes a unique epitope with a signature motif common across coronaviruses |
| title_full_unstemmed | A broadly neutralizing antibody recognizes a unique epitope with a signature motif common across coronaviruses |
| title_short | A broadly neutralizing antibody recognizes a unique epitope with a signature motif common across coronaviruses |
| title_sort | broadly neutralizing antibody recognizes a unique epitope with a signature motif common across coronaviruses |
| url | https://doi.org/10.1038/s41467-025-63101-1 |
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