ArticleNature communications2025
Orphan broadly RBD-binding antibodies annotate three remaining conserved RBD epitopes along SARS-CoV-2 evolution.
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Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed.
- Localized Rigidification and Allosteric Modulation Mechanisms of SARS-CoV-2 Spike Neutralization by Class 3 and Class 4 Antibodies at Atomic Resolution: An Integrated Computational Study of Binding, Dynamics, and Allostery.bioRxiv : the preprint server for biology · 2026Article
- Mechanisms of Binding and Immune Escape Resistance for Broadly Neutralizing Antibodies Targeting Distinct Conserved SARS-CoV-2 Spike Epitopes: A Hierarchical Approach Integrating Mutational Profiling and Energy Landscape Analysis.International journal of molecular sciences · 2026Article
- Frustration Landscapes of Broadly Neutralizing SARS-CoV-2 Spike Antibodies Targeting Conserved Epitopes Reveal Energetic Logic of Escape-Proof and Escape-Prone Mechanisms.bioRxiv : the preprint server for biology · 2026Article
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29 authors.
Minxiang Xie *Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0003-0108-9556
Yinong Qiu *Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Xiaoyu Zhao *Shanghai Sci-Tech Inno Center for Infection & Immunity, National Medical Center for Infectious Diseases, Huashan Hospital, Institute of Infection and Health, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-0347-9104
Jialu Shi *State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, Hong Kong, China.
Yuanchen Liu *State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, Hong Kong, China.
Qingsong Zhang *Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Jiaying He *Microbiological Testing Department, Baoshan District Center for Disease Control and Prevention, Shanghai, China.
Jiayan Li *Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai Institute of Infectious Disease and Biosecurity, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Fudan University, Shanghai, China.
Luotian LiuKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Siyuan SunKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Yuzhen ZhuDepartment of gastroenterology, Jingan District Central Hospitals, Fudan University, Shanghai, China.
Qiyu MaoKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Yiming LongKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Thiago Y OliveiraLaboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.ORCID http://orcid.org/0000-0002-2654-0879
Zijun WangLaboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.ORCID http://orcid.org/0000-0002-2095-2151
Yunjiao ZhouFundamental Research Center, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai, China.
Yan YanKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Anqi XiaKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Wenjing ZaiKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Christian T MayerExperimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-0256-9650
Youhua XieKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-2416-7708
Shibo JiangKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0001-8283-7135
Lu LuKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-2255-0391
Rong XiaDepartment of Transfusion Medicine, Shanghai Huashan Hospital, Fudan University, Shanghai, China. xiarongcn@126.com.ORCID http://orcid.org/0009-0008-2795-4740
Fan WuKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China. wufan@shmu.edu.cn.ORCID http://orcid.org/0000-0003-1039-3752
Lei SunKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China. llsun@fudan.edu.cn.ORCID http://orcid.org/0000-0001-8741-0202
Pengfei WangShanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai Institute of Infectious Disease and Biosecurity, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Fudan University, Shanghai, China. pengfei_wang@fudan.edu.cn.ORCID http://orcid.org/0000-0003-2454-7652
Hin ChuState Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, Hong Kong, China. hinchu@hku.hk.ORCID http://orcid.org/0000-0003-2855-9837
Qiao WangKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China. wangqiao@fudan.edu.cn.ORCID http://orcid.org/0000-0001-6416-1733
Funding
No grant is acknowledged in the PubMed record.
Abstract
The receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein continues to evolve, facilitating antibody evasion. It remains unclear whether any conserved RBD epitopes persist across SARS-CoV-2 variants and whether vaccination and/or breakthrough infection (BTI) can elicit antibodies capable of targeting these conserved regions to counter future variants. Here, using a heterogeneous double-bait single B-cell sorting strategy, we identify a subset of antibodies with broad-spectrum RBD binding, including recognition of SARS-CoV-1 and emerging variants such as EG.5.1, BA.2.86, JN.1, and KP.2/3. These broadly binding antibodies (bbAbs) exhibit elevated levels of somatic hypermutation but are infrequently derived from clonally expanded B lymphocytes. Passive transfer of representative bbAbs reduces viral infection in a male hamster model. Structural analyses reveals that these bbAbs primarily target three distinct, highly conserved RBD epitopes, suggesting potential regions of future mutational pressure and highlighting the presence of conserved and immunogenic RBD conformations that may serve as a foundation for the development of broadly protective vaccines.
Indexed as
Antibodies, ViralCOVID-19EpitopesSARS-CoV-2Spike Glycoprotein, CoronavirusAnimalsAntibodies, NeutralizingB-LymphocytesConserved SequenceCricetinaeEvolution, MolecularHumansMaleProtein DomainsAntibodies, NeutralizingAntibodies, ViralEpitopesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2
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