| Author |
Yuka Takumi-Tanimukai, Soh Yamamoto, Yurie Yoshida, Tatsuki Takahashi, Akira Takasawa, Akira Katsuyama, Takumi Nishimaki, Haruka Maeda, Katsumi Mizuta, Masashi Idogawa, Yukari Mitsuhashi, Yume Takayanagi, Sithumini M. W. Lokupathirage, Keitaro Yoshida, Keisuke Yamamoto, Takuya Kakuki, Sumito Jitsukawa, Toyotaka Sato, Hirofumi Sawa, Yasuko Orba, Akihiko Sato, Takashi Kojima, Wataru Kamitani, Satoshi Ichikawa, Tetsuya Nosaka, Kenichi Takano, Shin-ichi Yokota, Noriko Ogasawara
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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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