{
  "abstract": "The continual emergence of SARS-CoV-2 variants that rapidly evade conventional spike-directed neutralizing antibodies, together with the ongoing risk of cross-species spillover and new sarbecovirus outbreaks, underscores the need to develop broadly acting, escape-resistant therapeutic agents. Here, we optimized a nanobody discovery pipeline incorporating competition-based yeast surface display assays to isolate single-chain variable heavy chain-only antibody domains (VHHs or nanobodies) that bind human ACE2 and inhibit SARS-CoV-2 entry. Dimeric VHHs, as well as bivalent and tetravalent Fc-fusion proteins exhibited markedly increased antiviral activity, blocking a broad panel of SARS-CoV-2 variants and diverse sarbecoviruses at low-nanomolar to picomolar concentrations. These agents did not affect ACE2 enzymatic function or cell surface expression. The VHH-Fc fusion proteins had favorable pharmacokinetics and conferred prophylactic protection in mouse models of both SARS-CoV-2 and SARS-CoV infection, showcasing their potential as broadly acting receptor-targeted biologics against pandemic-threat viruses.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "A. D. Bakasis"
    },
    {
      "name": "R. Patejak"
    },
    {
      "name": "P. C. Fridy"
    },
    {
      "name": "J. Jenkins"
    },
    {
      "name": "M. Aldis"
    },
    {
      "name": "V. A. Baharani"
    },
    {
      "name": "L. Sriram"
    },
    {
      "name": "K. R. Molloy"
    },
    {
      "name": "B. T. Chait"
    },
    {
      "name": "M. P. Rout"
    },
    {
      "name": "F. R. Cross"
    },
    {
      "name": "P. D. Bieniasz"
    },
    {
      "affs": [
        0
      ],
      "name": "T. Hatziioannou"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2qa1mp2gx7xq8.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.01.748598",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748598v1.full",
  "id": "2qa1mp2gx7xq8",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748598v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2725|SARS-CoV-2 and COVID-19 Research"
    ]
  ],
  "openalex": "W7208769551",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748598v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2qa1mp2gx7xq8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:12Z",
      "native_id": "10.64898/2026.09.01.748598",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748598v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Multivalent Anti-ACE2 Nanobodies Confer Broad Pan-Sarbecovirus Protection",
  "title_text": "Multivalent Anti-ACE2 Nanobodies Confer Broad Pan-Sarbecovirus Protection",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:12Z",
  "url": "https://research.draconitic.com/paper/2qa1mp2gx7xq8",
  "venue": "bioRxiv",
  "versions": []
}