Ondansetron exhibits potent antiviral activity against enterovirus 71 infection in vitro and in vivo

  • Virus Res. 2026 Aug:370:199771. doi: 10.1016/j.virusres.2026.199771.
Zhenyang Li  1 ,  Jianqiao Rui  1 ,  Jiazheng Li  2 ,  Sichen Ren  2 ,  Yan Luo  2 ,  Weiyan Zhu  1 ,  Huimin Tao  1 ,  Mingzhu Guo  1 ,  Qingsong Dai  1 ,  Wan Peng  1 ,  Siqi Li  1 ,  Xiaojia Guo  1 ,  Wei Li  1 ,  Jingjing Yang  3 ,  Ruiyuan Cao  4 ,  Wu Zhong  5
Affiliations
  • 1. Academy of Military Medical Sciences, Beijing 100850, China; National Engineering Research Center for the Emergency Drug, Beijing 100039, China.
  • 2. Song Li's Academician Workstation, School of Pharmaceutical Sciences, Hainan University, Yazhou Bay, Sanya 572000, China.
  • 3. Academy of Military Medical Sciences, Beijing 100850, China; National Engineering Research Center for the Emergency Drug, Beijing 100039, China; Song Li's Academician Workstation, School of Pharmaceutical Sciences, Hainan University, Yazhou Bay, Sanya 572000, China. Electronic address: [email protected].
  • 4. Academy of Military Medical Sciences, Beijing 100850, China; National Engineering Research Center for the Emergency Drug, Beijing 100039, China. Electronic address: [email protected].
  • 5. Academy of Military Medical Sciences, Beijing 100850, China; National Engineering Research Center for the Emergency Drug, Beijing 100039, China. Electronic address: [email protected].
PMID: 42349797 DOI: 10.1016/j.virusres.2026.199771
Abstract

Enterovirus A71 (EV-A71) is a major causative agent of hand, foot, and mouth disease (HFMD) with neurotropism, and currently no approved Antiviral therapies are available. In this study, we found that the ondansetron exhibits Antiviral activity against EV-A71 Infection. Ondansetron significantly reducing viral RNA levels, progeny virus production, and VP1 protein expression in a dose-dependent manner. In vivo, ondansetron treatment increased survival of neonatal mice and decreased viral loads in multiple tissues. Mechanistically, ondansetron modulates Cholesterol metabolism-related genes to affect cell Cholesterol stability and interferes with viral attachment during the early stage of Infection, thereby inhibiting EV-A71 Infection. These findings indicate that ondansetron is a promising candidate for drug repurposing to treat EV-A71 Infection.

Keywords
Cholesterol metabolism; Drug repurposing; Enterovirus A71; Host-targeting; Viral attachment.
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