{
  "abstract": "Nucleoside analogues are among the most promising broad-spectrum antiviral agents. We developed a high-throughput synergistic screening system to identify US Food and Drug Administration-approved drugs that enhance the effectiveness of nucleoside analogues. Unlike conventional combination approaches, this strategy does not require boost agents to have direct antiviral activity; instead, they can enhance antiviral agent's effect through novel synergistic mechanisms. We identified mycophenolate mofetil (MMF), which significantly boosts ribavirin's (RBV) antiviral efficacy against influenza A virus, even at concentrations where MMF alone shows minimal activity. MMF enhances RBV by inhibiting IMPDH (inosine-5'-monophosphate dehydrogenase) and reducing cellular GTP levels, potentially increasing RBV incorporation and its antiviral potency. This mechanism was confirmed by adding exogenous GTP, which reversed the synergy. In a mouse model, MMF also enhanced RBV's effectiveness against PR8 in vivo. Moreover, MMF showed synergistic effects against other influenza subtypes and RNA viruses including ZIKV and HCoV-OC43, demonstrating the potential wide applicability of this strategy. Our study introduces a new screening system and identifies novel RBV combinations, offering a promising approach for developing effective broad-spectrum antiviral combinations against emerging viral threats.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou National Laboratory Clinical Base, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China.",
    "Guangzhou National Laboratory, Department of Basic Research, Guangzhou 510005, China.",
    "Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.",
    "University of the Chinese Academy of Sciences, Beijing 100049, China.",
    "Qingdao Academy of Chinese Medical Sciences, Shandong University of Traditional Chinese Medicine, Qingdao 266122, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Qiangyun Ai"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Huina Hu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Kaixiong Ma"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Qingxing Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Shenglin Huang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yongzhi Lu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Nan Qi"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jinsai Shang"
    },
    {
      "affs": [
        4
      ],
      "name": "Ruikun Du"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Shaobo Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a3wcabnhgj3e5.bib",
  "cited_by": 0,
  "doi": "10.1016/j.apsb.2026.05.017",
  "fulltext_url": "https://europepmc.org/articles/PMC13712292",
  "id": "a3wcabnhgj3e5",
  "issns": [
    "2211-3835",
    "2211-3843"
  ],
  "landing_url": "https://europepmc.org/article/MED/42948370",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "1312|Biochemical and Molecular Research"
    ]
  ],
  "openalex": "W7161807859",
  "pdf_url": "https://europepmc.org/articles/PMC13712292?pdf=render",
  "pmcid": "PMC13712292",
  "pmid": "42948370",
  "published": "2026-05-20",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/a3wcabnhgj3e5.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:36Z",
      "native_id": "MED:42948370",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42948370"
    },
    {
      "first_seen": "2026-10-31T12:22:54Z",
      "native_id": "PMC13712292",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.apsb.2026.05.017"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Biochemical and Molecular Research",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Identification of FDA-approved IMPDH inhibitors boosting the broad-spectrum antiviral potential of ribavirin through depleting cellular GTP pool.",
  "title_text": "Identification of FDA-approved IMPDH inhibitors boosting the broad-spectrum antiviral potential of ribavirin through depleting cellular GTP pool.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:22:54Z",
  "url": "https://research.draconitic.com/paper/a3wcabnhgj3e5",
  "venue": "Acta pharmaceutica Sinica. B",
  "versions": []
}