{
  "abstract": "The continuing evolution of SARS-CoV-2 variants of concern, and the increasing spillover potential of sarbecoviruses into the human population presents an important and urgent need to discover cross-reactive monoclonal antibodies (mAbs) for future therapeutic use and identify conserved neutralising epitopes that can be used for rationale design of broadly protective sarbecovirus vaccines. Here we study the neutralising epitopes on WIV-1 Spike of three mAbs that confer broad sarbecovirus and SARS-CoV-2 variant neutralisation, including XEC, JN.1, and XFG. mAb V1WT_06 binds a highly conserved RBD site V epitope that is mediated by the heavy chain alone. V1WT_06 contact residues are highly conserved in circulating viruses suggesting that the epitope is evolutionarily and functionally constrained. mAbs V1WT_41 and VA14_26 bind overlapping RBD class 4 epitopes with differing angles of approach that impact on the degree of ACE2 competition. We show that neutralisation by these mAbs is maintained when virus entry is via Japanese horseshoe bat and Halcyon horseshoe bat ACE2s. These mAbs are ideal candidates for therapeutic antibody development and inform the rational design of pan-betacoronavirus vaccines.\n\nThe increasing spillover risk of sarbecoviruses into humans stresses the urgent need to identify cross-reactive antibodies with therapeutic potential. This study uncovers the mechanisms of broad sarbecovirus cross-reactivity of three human antibodies that can inform the rational design of therapeutic antibodies and pan-coronavirus vaccines.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Infectious Diseases, School of Immunology & Microbial Sciences, King’s College London, London, United Kingdom",
    "Chromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute, London, United Kingdom",
    "The Pirbright Institute, Woking, Surrey, United Kingdom",
    "Structural Biology Science Technology Platform, The Francis Crick Institute, London, United Kingdom",
    "MRC-University of Glasgow Centre for Virus Research, The University of Glasgow, Glasgow, United Kingdom",
    "Department of Infectious Disease, South Kensington Campus, Imperial College London, London, United Kingdom"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ayush Upadhyay"
    },
    {
      "affs": [
        1
      ],
      "name": "Jeffrey Seow"
    },
    {
      "affs": [
        2
      ],
      "name": "Yilmaz Alguel"
    },
    {
      "affs": [
        3
      ],
      "name": "Joseph Newman"
    },
    {
      "affs": [
        4
      ],
      "name": "Nazia Thakur"
    },
    {
      "affs": [
        5
      ],
      "name": "Abigail L. Hay"
    },
    {
      "name": "Jerry C. H. Tam"
    },
    {
      "name": "Andrea Nans"
    },
    {
      "name": "Richard J. Orton"
    },
    {
      "name": "Dalan Bailey"
    },
    {
      "name": "Peter Cherepanov"
    },
    {
      "name": "Katie J. Doores"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/169y6jkbhkknx.bib",
  "cited_by": 1,
  "doi": "10.1371/journal.pbio.3003882",
  "fulltext_url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003882",
  "id": "169y6jkbhkknx",
  "issns": [
    "1545-7885"
  ],
  "landing_url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003882",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2725|SARS-CoV-2 and COVID-19 Research"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Immune system proteins/Antibodies"
    ],
    [
      "plos",
      "/Biology and life sciences/Immunology/Clinical immunology/Antibody therapy"
    ],
    [
      "plos",
      "/Biology and life sciences/Immunology/Immune system proteins/Antibodies"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Viral pathogens/Coronaviruses/SARS coronavirus/SARS CoV 2"
    ],
    [
      "plos",
      "/Biology and life sciences/Molecular biology/Molecular biology techniques/Transfection"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Viruses/RNA viruses/Coronaviruses/SARS coronavirus/SARS CoV 2"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Viruses/Viral pathogens/Coronaviruses/SARS coronavirus/SARS CoV 2"
    ],
    [
      "plos",
      "/Biology and life sciences/Physiology/Immune physiology/Antibodies"
    ],
    [
      "plos",
      "/Biology and life sciences/Physiology/Physiological processes/Molting"
    ],
    [
      "plos",
      "/Medicine and health sciences/Clinical medicine/Clinical immunology/Antibody therapy"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Clinical immunology/Antibody therapy"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune system proteins/Antibodies"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancer treatment/Antibody therapy"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Viral pathogens/Coronaviruses/SARS coronavirus/SARS CoV 2"
    ],
    [
      "plos",
      "/Research and analysis methods/Immunologic techniques/Immunoassays/Enzyme-linked immunoassays"
    ],
    [
      "plos",
      "/Research and analysis methods/Microscopy/Electron microscopy/Electron cryo-microscopy"
    ],
    [
      "plos",
      "/Research and analysis methods/Molecular biology techniques/Transfection"
    ],
    [
      "plos",
      "/Research and analysis methods/Spectrum analysis techniques/Spectrophotometry/Cytophotometry/Flow cytometry"
    ]
  ],
  "openalex": "W7215133107",
  "pdf_url": "https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3003882&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/169y6jkbhkknx.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:37Z",
      "native_id": "10.1371/journal.pbio.3003882",
      "source": "plos",
      "url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003882"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:immunology",
      "subfield": "immunology"
    },
    {
      "field": "medicine",
      "origin": "plos:physiology",
      "subfield": "physiology"
    }
  ],
  "title": "Targeting of conserved spike epitopes enables broad antibody neutralisation of diverse bat sarbecoviruses",
  "title_text": "Targeting of conserved spike epitopes enables broad antibody neutralisation of diverse bat sarbecoviruses",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:37Z",
  "url": "https://research.draconitic.com/paper/169y6jkbhkknx",
  "venue": "PLOS Biology",
  "versions": []
}