{
  "abstract": "The rapid mutation of the SARS-CoV-2 spike (S) protein promotes immune evasion and challenges current therapeutics. However, its cysteine/disulfide bond pattern is highly conserved across coronaviruses and essential for its structure and function. Here, we demonstrate that the folding and maturation of the S protein is a redox-sensitive process managed by sulfhydryl oxidase Ero1α and protein disulfide isomerase (PDI) in the endoplasmic reticulum. Reducing agents or cysteine mutations inhibit furin-processing of the S protein and its transport to the plasma membrane. Genetic or pharmacological disruption of the Ero1α-PDI pathway impairs S protein oxidative folding, furin cleavage and plasma membrane localization, as well as its fusogenic activity. Using a SARS-CoV-2 reverse genetics model, we confirm that targeting the Ero1α-PDI pathway exhibits potent antiviral effect. Moreover, the Ero1α-PDI pathway is essential for S protein maturation across different β-coronaviruses. Thus, our findings highlight the oxidative protein folding machinery as a promising target for developing broad-spectrum anti-coronavirus therapies.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.",
    "State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.",
    "State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address: wangxi@ibp.ac.cn.",
    "State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address: wanglei@ibp.ac.cn."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xinqian Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Ping Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Xi'e Wang"
    },
    {
      "affs": [
        2
      ],
      "name": "Xi Wang"
    },
    {
      "affs": [
        3
      ],
      "name": "Lei Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cqy9s4n100ay8.bib",
  "cited_by": 0,
  "doi": "10.1016/j.redox.2026.104427",
  "fulltext_url": "https://europepmc.org/articles/PMC13676017",
  "id": "cqy9s4n100ay8",
  "issns": [
    "2213-2317"
  ],
  "landing_url": "https://europepmc.org/article/MED/42843276",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1307|Endoplasmic Reticulum Stress and Disease"
    ]
  ],
  "openalex": "W7220447085",
  "pdf_url": "https://europepmc.org/articles/PMC13676017?pdf=render",
  "pmcid": "PMC13676017",
  "pmid": "42843276",
  "published": "2026-10-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/cqy9s4n100ay8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:10Z",
      "native_id": "MED:42843276",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42843276"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Endoplasmic Reticulum Stress and Disease",
      "subfield": "cell-biology"
    }
  ],
  "title": "Targeting the Ero1α-PDI oxidative protein folding pathway as a broad-spectrum strategy against coronavirus.",
  "title_text": "Targeting the Ero1α-PDI oxidative protein folding pathway as a broad-spectrum strategy against coronavirus.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:10Z",
  "url": "https://research.draconitic.com/paper/cqy9s4n100ay8",
  "venue": "Redox biology",
  "versions": []
}