{
  "abstract": "Respiratory syncytial virus (RSV) causes substantial respiratory disease, while treatment is limited by drug resistance. Molecular docking of a 3,880-compound natural-product library identifies punicalin (PUN) as a dual-target RSV entry inhibitor. PUN inhibits the evaluated RSV-A and RSV-B strains, including a clinical isolate, and retains activity against strains resistant to ziresovir, ribavirin, nirsevimab, and palivizumab. After 20 passages under PUN selection, the half-maximal inhibitory concentration (IC50) increases 3.88-fold, remaining below the predefined >10-fold resistance threshold. Mechanistic analyses suggest that PUN interacts with the G protein cystine-noose region involving N178, N179, and W183 to inhibit attachment and with an F protein region involving V243, T245, and P246 to stabilize prefusion F and inhibit membrane fusion. These regions do not overlap known resistance hotspots. In RSV-infected mice, nebulized PUN provides sustained respiratory exposure, reduces lung viral loads and pathology, and attenuates inflammatory responses.",
  "abstract_shown": true,
  "affiliations": [
    "Jiangsu Key Laboratory of Children’s Health and Chinese Medicine, The First Clinical College, Nanjing University of Chinese Medicine, Nanjing, China",
    "The State Key Laboratory of Pharmaceutical Biotechnology, Chemistry and Biomedicine Innovation Center (ChemBIC), Division of Immunology, Medical School, Nanjing University, Nanjing 210093, China",
    "School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China",
    "Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine, Zhongnan West Road, Wuxi 214071, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Yingcai Xiong"
    },
    {
      "affs": [
        0
      ],
      "name": "Jingyi Ming"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhaowei Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiru Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoqing Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Biyu Cao"
    },
    {
      "affs": [
        2
      ],
      "name": "Guang Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuqing Zhu"
    },
    {
      "affs": [
        0
      ],
      "name": "Zepeng Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Junxi Song"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhao Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Mei Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Keyu Tao"
    },
    {
      "affs": [
        2
      ],
      "name": "Yue Kang"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Jianjian Ji"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/04ke207xncadc.bib",
  "cited_by": 0,
  "doi": "10.1016/j.xcrm.2026.103078",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13710551/",
  "id": "04ke207xncadc",
  "issns": [
    "2666-3791"
  ],
  "landing_url": "https://doi.org/10.1016/j.xcrm.2026.103078",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2713|Respiratory viral infections research"
    ]
  ],
  "openalex": "W7214303496",
  "pdf_url": null,
  "pmcid": "PMC13710551",
  "pmid": "42790425",
  "published": "2026-09-25",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/04ke207xncadc.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:30Z",
      "native_id": "PMC13710551",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.xcrm.2026.103078"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Respiratory viral infections research",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Punicalin targets RSV glycoprotein and fusion protein at non-overlapping sites to prevent viral escape",
  "title_text": "Punicalin targets RSV glycoprotein and fusion protein at non-overlapping sites to prevent viral escape",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:30Z",
  "url": "https://research.draconitic.com/paper/04ke207xncadc",
  "venue": "Cell Reports Medicine",
  "versions": []
}