{
  "abstract": "Zika virus (ZIKV) substantially relies on host lipid metabolism, presenting a prime target for host-directed antivirals. To identify host-directed antiviral interventions while circumventing interferon-mediated transcriptomic masking, we curated a dual-virus (dengue and ZIKV) gene signature to query the Connectivity Map. Top lipid-lowering candidates were validated using a reporter virus (rZIKV-Venus) and an authentic wild-type (WT) ZIKV in Vero E6 cells—a model deliberately selected for its interferon deficiency to isolate pure metabolic responses. Dose–response screening of 67 prioritized compounds identified atorvastatin, rosuvastatin, and clofibrate as potent ZIKV inhibitors. Statin–clofibrate combinations exhibited strong synergy, with fractional inhibitory concentration index (FICI) values of 0.203 (atorvastatin–clofibrate) and 0.117 (rosuvastatin–clofibrate) for the 4:1 clofibrate-to-statin ratio and an optimized selectivity index. Mechanistically, exogenous oleic acid supplementation induced significant metabolic complementation, significantly restoring both host lipid droplet (LD) abundance and ZIKV replication readouts suppressed by the dual treatment. Relative LD intensity strongly correlated with viral intensity in both models (Pearson r = 0.951 and 0.956, respectively; both p < 0.0001). These findings demonstrate that concurrent pharmacological modulation of host lipid metabolism exerts synergistic anti-ZIKV effects, highlighting highly curated transcriptomic repurposing as a mechanistic prioritization strategy for host-directed antiviral discovery.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Veterinary Pathology, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, Republic of Korea",
    "Animal Medical Institute, Chonnam National University, Gwangju 61186, Republic of Korea",
    "Department of Veterinary Pathology, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Republic of Korea",
    "Department of Food and Environmental Hygiene, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Republic of Korea",
    "Texas Biomedical Research Institute, San Antonio, TX 78227, USA",
    "Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, Campus Cantoblanco UAM, 28049 Madrid, Spain",
    "Department of Veterinary Zoonotic Diseases, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Republic of Korea"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Chung-Do Lee",
      "orcid": "0009-0002-1029-5669"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Sang-Ik Park",
      "orcid": "0000-0003-1709-0324"
    },
    {
      "affs": [
        2
      ],
      "name": "Gun Lee",
      "orcid": "0009-0003-5545-4464"
    },
    {
      "affs": [
        2
      ],
      "name": "Hyeon Jeong Moon",
      "orcid": "0009-0007-0943-9297"
    },
    {
      "affs": [
        0
      ],
      "name": "Jaewoo Choi"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Jun Bong Lee"
    },
    {
      "affs": [
        4
      ],
      "name": "Luis Martinez-Sobrido",
      "orcid": "0000-0001-7084-0804"
    },
    {
      "affs": [
        5
      ],
      "name": "Fernando Almazán",
      "orcid": "0000-0002-5752-8469"
    },
    {
      "affs": [
        6
      ],
      "name": "Eun-Hye Ryu"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Yeong-Bin Baek",
      "orcid": "0000-0003-1703-7742"
    },
    {
      "affs": [
        1,
        6
      ],
      "name": "Jun-Gyu Park",
      "orcid": "0000-0001-7163-3591"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fbjfgkn964qja.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27219637",
  "fulltext_url": null,
  "id": "fbjfgkn964qja",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/9637",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2739|Mosquito-borne diseases and control"
    ]
  ],
  "openalex": "W7224113632",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-28",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/fbjfgkn964qja.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:57Z",
      "native_id": "10.3390/ijms27219637",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/9637"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2739|Mosquito-borne diseases and control",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Synergistic Anti-Zika Activity of Repurposed Statin and Clofibrate Combinations: Evidence from Oleic Acid-Mediated Metabolic Complementation",
  "title_text": "Synergistic Anti-Zika Activity of Repurposed Statin and Clofibrate Combinations: Evidence from Oleic Acid-Mediated Metabolic Complementation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:57Z",
  "url": "https://research.draconitic.com/paper/fbjfgkn964qja",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}