{
  "abstract": "Powassan virus (POWV) is an emerging tick-borne orthoflavivirus that causes severe encephalitis, long-term neurologic sequelae, and death, yet no approved antiviral therapies exist. Here, we evaluated several previously characterized nucleoside analogs as candidate countermeasures for POWV encephalitis. Favipiravir, molnupiravir, 4'-fluorouridine (4'-FlU), and GS-441524 inhibited POWV replication in vitro and demonstrated comparable activity against West Nile virus (WNV). We established C3H/HeNCrl mice as a stringent POWV disease model, showing increased susceptibility, higher day 7 brain titers, and more pronounced neurologic signs resembling severe human disease, compared with C57BL/6 mice. In prophylactic and therapeutic studies, 4'-fluorouridine was the most efficacious compound tested, significantly reducing brain viral burden even when treatment was delayed. Direct comparison with molnupiravir, favipiravir, and GS-441524 in mice confirmed superior survival benefit and antiviral activity for 4'-FlU against both POWV and WNV. These data identify 4'-fluorouridine as a promising therapeutic candidate for neurotropic flavivirus disease.",
  "abstract_shown": true,
  "affiliations": [
    "Georgia State University Institute for Biomedical Sciences"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "D. S. M. Lewis"
    },
    {
      "name": "T. Moore"
    },
    {
      "name": "R. Patel"
    },
    {
      "affs": [
        0
      ],
      "name": "R. Cox"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9e88gjdrzvnjt.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.24.754293",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754293v1.full",
  "id": "9e88gjdrzvnjt",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754293v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "microbiology"
    ],
    [
      "openalex",
      "2725|Viral Infections and Vectors"
    ]
  ],
  "openalex": "W7214457872",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754293v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9e88gjdrzvnjt.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:39Z",
      "native_id": "10.64898/2026.09.24.754293",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754293v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "Potency of nucleoside analogs against Powassan virus replication and identification of 4'-fluorouridine as a therapeutic candidate for tick-borne orthoflavivirus encephalitis",
  "title_text": "Potency of nucleoside analogs against Powassan virus replication and identification of 4'-fluorouridine as a therapeutic candidate for tick-borne orthoflavivirus encephalitis",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:39Z",
  "url": "https://research.draconitic.com/paper/9e88gjdrzvnjt",
  "venue": "bioRxiv",
  "versions": []
}