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Peer-reviewedCC BYCommunications biology

Sparfloxacin reveals a host-virus dual-target antiviral scaffold against respiratory syncytial virus.

  • Yuka Takumi-Tanimukai1,2
  • Soh Yamamoto1
  • Yurie Yoshida1,2
  • Tatsuki Takahashi3
  • Akira Takasawa4
  • Akira Katsuyama5,6,7
  • Takumi Nishimaki1,8
  • Haruka Maeda9,10
  • Katsumi Mizuta11
  • Masashi Idogawa12
  • Yukari Mitsuhashi1
  • Yume Takayanagi1,2
16 more authors
  • Sithumini M W Lokupathirage1
  • Keitaro Yoshida1
  • Keisuke Yamamoto1,2
  • Takuya Kakuki2
  • Sumito Jitsukawa2
  • Toyotaka Sato1,13,14,15,16
  • Hirofumi Sawa9,15,17
  • Yasuko Orba9,17
  • Akihiko Sato9,10,17
  • Takashi Kojima18
  • Wataru Kamitani3
  • Satoshi Ichikawa5,6,7
  • Tetsuya Nosaka19,20
  • Kenichi Takano2
  • Shin-Ichi Yokota1
  • Noriko Ogasawara21,22
22 affiliations
  1. 1Division of Microbiology, Department of Infectious Diseases, Sapporo Medical University School of Medicine, Sapporo, Japan.
  2. 2Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
  3. 3Department of Infectious Diseases and Host Defense, Graduate School of Medicine, Gunma University, Maebashi, Japan.
  4. 4Division of Tumor Pathology, Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.
  5. 5Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
  6. 6Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
  7. 7Global Station for Biosurfaces and Drug Discovery, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan.
  8. 8Division of Respiratory Medicine and Allergology, Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
  9. 9International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.
  10. 10Laboratory for Drug Discovery & Disease Research, Shionogi & Co. Ltd, Osaka, Japan.
  11. 11Yamagata Prefectural Institute of Public Health, Yamagata, Japan.
  12. 12Division of Medical Genome Sciences, Department of Genomic and Preventive Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
  13. 13Laboratory of Veterinary Hygiene, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
  14. 14Graduate School of Infectious Diseases, Hokkaido University, Sapporo, Japan.
  15. 15One Health Research Center, Hokkaido University, Sapporo, Japan.
  16. 16Veterinary Research Unit, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.
  17. 17Institute for Vaccine Research and Development, Hokkaido University, Sapporo, Japan.
  18. 18Department of Cell Science, Institute of Cancer Research, Sapporo Medical University, Sapporo, Japan.
  19. 19Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu, Japan.
  20. 20Research Centre for Development of Recombinant VLP Vaccines, Research Institutes of Excellence, Mie University, Tsu, Japan.
  21. 21Division of Microbiology, Department of Infectious Diseases, Sapporo Medical University School of Medicine, Sapporo, Japan. [email protected].
  22. 22Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan. [email protected].
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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.

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Cite

BibTeXRIS
BibTeX
@article{takumitanimukai2026sparfloxacin,
  title = {{Sparfloxacin reveals a host-virus dual-target antiviral scaffold against respiratory syncytial virus.}},
  author = {Yuka Takumi-Tanimukai and Soh Yamamoto and Yurie Yoshida and Tatsuki Takahashi and Akira Takasawa and Akira Katsuyama and Takumi Nishimaki and Haruka Maeda and Katsumi Mizuta and Masashi Idogawa and Yukari Mitsuhashi and Yume Takayanagi and Sithumini M W Lokupathirage and Keitaro Yoshida and Keisuke Yamamoto and Takuya Kakuki and Sumito Jitsukawa and Toyotaka Sato and Hirofumi Sawa and Yasuko Orba and Akihiko Sato and Takashi Kojima and Wataru Kamitani and Satoshi Ichikawa and Tetsuya Nosaka and Kenichi Takano and Shin-Ichi Yokota and Noriko Ogasawara},
  journal = {Communications biology},
  year = {2026},
  month = aug,
  doi = {10.1038/s42003-026-10744-5},
  url = {https://europepmc.org/article/MED/42963363},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Sparfloxacin reveals a host-virus dual-target antiviral scaffold against respiratory syncytial virus.
AU  - Yuka Takumi-Tanimukai
AU  - Soh Yamamoto
AU  - Yurie Yoshida
AU  - Tatsuki Takahashi
AU  - Akira Takasawa
AU  - Akira Katsuyama
AU  - Takumi Nishimaki
AU  - Haruka Maeda
AU  - Katsumi Mizuta
AU  - Masashi Idogawa
AU  - Yukari Mitsuhashi
AU  - Yume Takayanagi
AU  - Sithumini M W Lokupathirage
AU  - Keitaro Yoshida
AU  - Keisuke Yamamoto
AU  - Takuya Kakuki
AU  - Sumito Jitsukawa
AU  - Toyotaka Sato
AU  - Hirofumi Sawa
AU  - Yasuko Orba
AU  - Akihiko Sato
AU  - Takashi Kojima
AU  - Wataru Kamitani
AU  - Satoshi Ichikawa
AU  - Tetsuya Nosaka
AU  - Kenichi Takano
AU  - Shin-Ichi Yokota
AU  - Noriko Ogasawara
PY  - 2026
DA  - 2026/08/08
JO  - Communications biology
DO  - 10.1038/s42003-026-10744-5
UR  - https://europepmc.org/article/MED/42963363
AB  - 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.
SN  - 2399-3642
ER  -