{
  "abstract": "Although Gasdermin A (GSDMA) drives inflammation by inducing pyroptosis, its specific role in antiviral defense remains unclear. Here we identify GSDMA as an immunomodulatory protein activated in response to coronavirus (CoV) infection. Specifically, CoV-encoded protease nsp5 cleaves GSDMA at two conserved glutamine sites, Q247 and Q187. Cleavage at Q247 liberates an active N-terminal fragment (GSDMA_1–247) that triggers pyroptosis, promotes inflammation, and restricts viral replication. In contrast, cleavage at the alternative site Q187 attenuates this function. Using Gsdma-/- mice, we show that GSDMA deficiency increases viral loads but reduces inflammation, tissue damage, and mortality upon infection. These findings suggest that disease severity is driven more by inflammation than by viral load. Our findings reveal a novel mechanism of antiviral immunity and inflammatory regulation via CoV nsp5-mediated dual cleavage of GSDMA, highlighting a potential target for combined antiviral and anti-inflammatory therapies. Author summary: Coronaviruses continue to threaten global health, as demonstrated by recent outbreaks. Gasdermin A (GSDMA) is a host protein involved in pyroptosis, which is an inflammatory cell death. In this study, we demonstrate that the coronavirus 3C-like protease cleaves GSDMA at two distinct sites, generating fragments with different functional properties. One cleavage product enhances inflammation and limits viral replication, whereas the other does not exhibit these activities. Our findings suggest that coronaviruses 3C-like proteases may regulate cleavage at these two sites to influence the relative abundance of the resulting fragments, thereby balancing antiviral defense and inflammatory responses. Using a mouse model, we further demonstrate that loss of GSDMA results in higher viral loads but reduced inflammatory pathology and improved survival. These observations indicate that disease severity may be more closely linked to the magnitude of the inflammatory response than to viral burden alone. Together, our work highlights the importance of targeting both viral replication and dysregulated inflammation in therapeutic strategies.",
  "abstract_shown": true,
  "affiliations": [
    "National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China",
    "The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China",
    "State Key Laboratory of Pharmaceutical Biotechnology, Ministry of Education Key Laboratory of Model Animal for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China",
    "Center of Animal Laboratory, Xuzhou Medical University, Xuzhou, China",
    "Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Chenyu Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Yuxi Zhao"
    },
    {
      "affs": [
        2
      ],
      "name": "Yuchen Zhang"
    },
    {
      "affs": [
        3
      ],
      "name": "Shuai Li"
    },
    {
      "affs": [
        4
      ],
      "name": "Longfei Chen"
    },
    {
      "name": "Xiangfei Xu"
    },
    {
      "name": "Tong Ding"
    },
    {
      "name": "Yuanqing Wang"
    },
    {
      "name": "Xiang Gao"
    },
    {
      "name": "Zhaoyu Lin"
    },
    {
      "name": "Guanning Su"
    },
    {
      "name": "Ankang Hu"
    },
    {
      "name": "Liurong Fang"
    },
    {
      "name": "Qi Su"
    },
    {
      "name": "Quangang Chen"
    },
    {
      "name": "Yanrong Zhou"
    },
    {
      "name": "Shaobo Xiao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/23j71ay7x647c.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.ppat.1014602",
  "fulltext_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014602",
  "id": "23j71ay7x647c",
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  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
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  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
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  "native_subjects": [
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      "openalex",
      "1312|Inflammasome and immune disorders"
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  "pdf_url": "https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1014602&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-16",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/23j71ay7x647c.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "10.1371/journal.ppat.1014602",
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      "url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014602"
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "plos:molecular biology",
      "subfield": "molecular-biology"
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    {
      "field": "biology",
      "origin": "plos:immunology",
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      "field": "biology",
      "origin": "plos:biotechnology",
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  "title": "Coronavirus Nsp5‑mediated dual‑site cleavage of GSDMA modifies its antiviral and proinflammatory functions",
  "title_text": "Coronavirus Nsp5‑mediated dual‑site cleavage of GSDMA modifies its antiviral and proinflammatory functions",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:49Z",
  "url": "https://research.draconitic.com/paper/23j71ay7x647c",
  "venue": "PLOS Pathogens",
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