{ "abstract": "Respiratory syncytial virus (RSV) is a major cause of severe respiratory illness across the lifespan, particularly in infants and older adults. Nonetheless, effective antiviral therapies remain limited. Here, we performed a clinically guided, medium-throughput screening of approved drugs used in pediatric populations and identified sparfloxacin (SPFX), a fluoroquinolone antibiotic, as a mechanistically informative antiviral scaffold. SPFX showed antiviral activity against genetically distinct RSV clinical isolates in vitro, and suppressed RSV infection in a mechanistic mouse model in vivo. Mechanistically, our findings support a host-virus dual-target framework in which SPFX suppresses RSV replication through activity consistent with modulation of viral RNA polymerase function together with a pro-viral HSP70-associated host pathway. Using primary human pediatric airway epithelial cells, we identified SPFX-responsive host factors and observed suppression of HSP70 expression independent of infection. Together, these findings establish SPFX as a mechanistically informative antiviral scaffold and support a host-virus dual-target framework for future RSV therapeutic development.", "abstract_shown": true, "affiliations": [ "Division of Microbiology, Department of Infectious Diseases, Sapporo Medical University School of Medicine, Sapporo, Japan.", "Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.", "Department of Infectious Diseases and Host Defense, Graduate School of Medicine, Gunma University, Maebashi, Japan.", "Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.", "Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.", "Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.", "Global Station for Biosurfaces and Drug Discovery, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan.", "Division of Respiratory Medicine and Allergology, Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.", "International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.", "Laboratory for Drug Discovery & Disease Research, Shionogi & Co. Ltd, Osaka, Japan.", "Yamagata Prefectural Institute of Public Health, Yamagata, Japan.", "Division of Medical Genome Sciences, Department of Genomic and Preventive Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.", "Laboratory of Veterinary Hygiene, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.", "Graduate School of Infectious Diseases, Hokkaido University, Sapporo, Japan.", "One Health Research Center, Hokkaido University, Sapporo, Japan.", "Veterinary Research Unit, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.", "Institute for Vaccine Research and Development, Hokkaido University, Sapporo, Japan.", "Department of Cell Science, Institute of Cancer Research, Sapporo Medical University, Sapporo, Japan.", "Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu, Japan.", "Research Centre for Development of Recombinant VLP Vaccines, Research Institutes of Excellence, Mie University, Tsu, Japan.", "Division of Microbiology, Department of Infectious Diseases, Sapporo Medical University School of Medicine, Sapporo, Japan. ogasawara.n@sapmed.ac.jp.", "Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan. ogasawara.n@sapmed.ac.jp." ], "article_type": "research article", "arxiv": null, "author_total": 28, "authors": [ { "affs": [ 0, 1 ], "name": "Yuka Takumi-Tanimukai" }, { "affs": [ 0 ], "name": "Soh Yamamoto" }, { "affs": [ 0, 1 ], "name": "Yurie Yoshida" }, { "affs": [ 2 ], "name": "Tatsuki Takahashi" }, { "affs": [ 3 ], "name": "Akira Takasawa" }, { "affs": [ 4, 5, 6 ], "name": "Akira Katsuyama", "orcid": "0000-0002-4062-5561" }, { "affs": [ 0, 7 ], "name": "Takumi Nishimaki" }, { "affs": [ 8, 9 ], "name": "Haruka Maeda", "orcid": "0009-0001-7769-0412" }, { "affs": [ 10 ], "name": "Katsumi Mizuta" }, { "affs": [ 11 ], "name": "Masashi Idogawa", "orcid": "0000-0002-8507-1726" }, { "affs": [ 0 ], "name": "Yukari Mitsuhashi" }, { "affs": [ 0, 1 ], "name": "Yume Takayanagi" }, { "affs": [ 0 ], "name": "Sithumini M W Lokupathirage" }, { "affs": [ 0 ], "name": "Keitaro Yoshida", "orcid": "0000-0002-5017-8566" }, { "affs": [ 0, 1 ], "name": "Keisuke Yamamoto" }, { "affs": [ 1 ], "name": "Takuya Kakuki" }, { "affs": [ 1 ], "name": "Sumito Jitsukawa" }, { "affs": [ 0, 12, 13, 14, 15 ], "name": "Toyotaka Sato", "orcid": "0000-0001-7223-1623" }, { "affs": [ 8, 14, 16 ], "name": "Hirofumi Sawa", "orcid": "0000-0003-2569-2755" }, { "affs": [ 8, 16 ], "name": "Yasuko Orba", "orcid": "0000-0001-9910-3912" }, { "affs": [ 8, 9, 16 ], "name": "Akihiko Sato", "orcid": "0000-0001-6625-1679" }, { "affs": [ 17 ], "name": "Takashi Kojima" }, { "affs": [ 2 ], "name": "Wataru Kamitani" }, { "affs": [ 4, 5, 6 ], "name": "Satoshi Ichikawa", "orcid": "0000-0001-5345-5007" }, { "affs": [ 18, 19 ], "name": "Tetsuya Nosaka", "orcid": "0000-0002-0037-7049" }, { "affs": [ 1 ], "name": "Kenichi Takano" }, { "affs": [ 0 ], "name": "Shin-Ichi Yokota", "orcid": "0000-0002-0831-3429" }, { "affs": [ 20, 21 ], "name": "Noriko Ogasawara", "orcid": "0000-0002-6014-3607" } ], "bibtex": "https://research.draconitic.com/paper/egg4e8dy4z38a.bib", "cited_by": 0, "doi": "10.1038/s42003-026-10744-5", "fulltext_url": "https://europepmc.org/articles/PMC13722688", "id": "egg4e8dy4z38a", "issns": [ "2399-3642" ], "landing_url": "https://europepmc.org/article/MED/42963363", "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", "Article" ], [ "openalex", "2713|Respiratory viral infections research" ] ], "openalex": "W7201980772", "pdf_url": "https://europepmc.org/articles/PMC13722688?pdf=render", "pmcid": "PMC13722688", "pmid": "42963363", "published": "2026-08-08", "publisher": "Nature Publishing Group", "ris": "https://research.draconitic.com/paper/egg4e8dy4z38a.ris", "sources": [ { "first_seen": "2026-11-02T03:21:43Z", "native_id": "MED:42963363", "source": "europepmc", "url": "https://europepmc.org/article/MED/42963363" }, { "first_seen": "2026-11-04T12:21:27Z", "native_id": "PMC13722688", "source": "pmc", "url": "https://doi.org/10.1038/s42003-026-10744-5" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2713|Respiratory viral infections research", "subfield": "epidemiology-public-health" } ], "title": "Sparfloxacin reveals a host-virus dual-target antiviral scaffold against respiratory syncytial virus.", "title_text": "Sparfloxacin reveals a host-virus dual-target antiviral scaffold against respiratory syncytial virus.", "type": "peer-reviewed", "updated_at": "2026-11-04T12:21:27Z", "url": "https://research.draconitic.com/paper/egg4e8dy4z38a", "venue": "Communications biology", "versions": [] }