{
  "abstract": "SARS-CoV-2 Omicron variants emerged in 2022 with >30 novel mutations in the spike alone. While most studies focus on receptor binding domain changes, mutations in the C-terminus of S1 (CTS1), adjacent to the furin cleavage site, have largely been ignored. Here, we examine three Omicron mutations in CTS1: H655Y, N679K, and P681H. Generating a SARS-CoV-2 triple mutant (YKH), we find that the mutant increases spike processing, consistent with prior reports for H655Y/P681H. In addition, the YKH mutant induces attenuated disease, but augments viral loads in male golden Syrian hamsters. Next, we generate a single N679K mutant, finding it reduces viral replication in Calu3 human respiratory cells and induces less disease in male golden Syrian hamsters. Mechanistically, the N679K mutant has increased spike processing but also reduces spike in purified virions; spike decreases are further exacerbated in infected Calu3 cell lysates. Importantly, exogenous spike expression reveals that N679K reduces overall spike protein in the context of the epidemic strain. Although a loss-of-function mutation, transmission competition demonstrates that N679K confers a replication advantage in the upper airway, potentially impacting transmissibility. Together, the data show that N679K reduces overall spike protein during Omicron infection, which has implications for infection, immunity, and transmission.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA",
    "Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, United States",
    "Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX, USA",
    "Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX, United States",
    "Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA",
    "Pediatrics, University of Texas Medical Branch, Galveston, TX, United States",
    "Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA",
    "Emory Vaccine Center, Emory University, Atlanta, GA, USA",
    "Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, United States",
    "Pathology, University of Texas Medical Branch, Galveston, TX, United States",
    "Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA",
    "Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston, TX, United States",
    "World Reference Center of Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, United States",
    "Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA",
    "World Reference Center of Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA",
    "Center for Biodefense and Emerging Infectious Disease, University of Texas Medical Branch, Galveston, TX, United States",
    "Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX, USA",
    "Department of Biochemistry and Microbiology, University of Texas Medical Branch, Galveston, TX, USA",
    "Department of Microbiology and Immunology, Scripps Research, La Jolla, CA, USA",
    "Institute of Microbiology, Chinese Academy of Sciences, Beijing, PR China",
    "Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA. vineet.d.menachery@emory.edu",
    "Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA. vineet.d.menachery@emory.edu",
    "Emory Vaccine Center, Emory University, Atlanta, GA, USA. vineet.d.menachery@emory.edu",
    "Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA. vineet.d.menachery@emory.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 23,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Michelle N. Vu",
      "orcid": "0000-0002-3208-710X"
    },
    {
      "affs": [
        0,
        2,
        3,
        1
      ],
      "name": "R. Elias Alvarado",
      "orcid": "0000-0002-1450-4854"
    },
    {
      "affs": [
        0,
        4,
        1,
        5
      ],
      "name": "Dorothea R. Morris",
      "orcid": "0000-0003-1049-2208"
    },
    {
      "affs": [
        0,
        6,
        7,
        1
      ],
      "name": "Kumari G. Lokugamage"
    },
    {
      "affs": [
        0,
        6,
        7,
        8
      ],
      "name": "Yiyang Zhou",
      "orcid": "0000-0001-8956-3229"
    },
    {
      "affs": [
        0,
        6,
        7,
        9
      ],
      "name": "Angelica L. Morgan"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yani P. Ahearn"
    },
    {
      "affs": [
        0,
        10,
        1
      ],
      "name": "Nicholas C. Hazell"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Leah K. Estes"
    },
    {
      "affs": [
        0,
        11,
        1,
        12
      ],
      "name": "Alyssa M. McLeland"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Craig Schindewolf",
      "orcid": "0000-0002-9804-2246"
    },
    {
      "affs": [
        0,
        13,
        14,
        9
      ],
      "name": "Jessica A. Plante",
      "orcid": "0000-0002-4768-7458"
    },
    {
      "affs": [
        10,
        1
      ],
      "name": "William M. Meyers"
    },
    {
      "affs": [
        0
      ],
      "name": "Jordan T. Murray"
    },
    {
      "affs": [
        10,
        15,
        11,
        1,
        12
      ],
      "name": "Patricia A. Crocquet-Valdes",
      "orcid": "0000-0002-2079-0076"
    },
    {
      "affs": [
        0,
        13,
        14,
        15,
        9
      ],
      "name": "Scott C. Weaver",
      "orcid": "0000-0001-8016-8556"
    },
    {
      "affs": [
        6,
        7,
        8
      ],
      "name": "Mehul S. Suthar",
      "orcid": "0000-0002-2686-8380"
    },
    {
      "affs": [
        16,
        10,
        8
      ],
      "name": "David Hughes Walker",
      "orcid": "0000-0002-3309-4360"
    },
    {
      "affs": [
        17,
        11,
        1,
        12
      ],
      "name": "William K. Russell",
      "orcid": "0000-0003-1931-4555"
    },
    {
      "affs": [
        18,
        15,
        11,
        1,
        12
      ],
      "name": "Andrew L. Routh",
      "orcid": "0000-0002-2874-5990"
    },
    {
      "affs": [
        16,
        0,
        10,
        19
      ],
      "name": "Haitao Hu"
    },
    {
      "affs": [
        0,
        10,
        13
      ],
      "name": "Kenneth S. Plante",
      "orcid": "0000-0002-7485-3167"
    },
    {
      "affs": [
        20,
        21,
        22,
        23
      ],
      "name": "Vineet D. Menachery",
      "orcid": "0000-0001-8803-7606"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/79saby2zahkq0.bib",
  "cited_by": 21,
  "doi": "10.1038/s41467-026-76680-4",
  "fulltext_url": null,
  "id": "79saby2zahkq0",
  "issns": [
    "2041-1723"
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  "landing_url": "https://doi.org/10.1038/s41467-026-76680-4",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "openalex",
      "2725|SARS-CoV-2 and COVID-19 Research"
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  "pdf_url": "https://www.nature.com/articles/s41467-026-76680-4_reference.pdf",
  "pmcid": "PMC10153209",
  "pmid": "37131784",
  "published": "2026-08-12",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/79saby2zahkq0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:54Z",
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      "url": "https://doi.org/10.1038/s41467-026-76680-4"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|SARS-CoV-2 and COVID-19 Research",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Loss-of-function mutation in Omicron variants reduces spike protein expression and attenuates SARS-CoV-2 infection",
  "title_text": "Loss-of-function mutation in Omicron variants reduces spike protein expression and attenuates SARS-CoV-2 infection",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:15Z",
  "url": "https://research.draconitic.com/paper/79saby2zahkq0",
  "venue": "Nature Communications",
  "versions": []
}