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April 21, 2026SHILAP Revista de lepidopterología0 citationsOpen Access

Genistein inhibits the replication of enterovirus A71

WHWenbo HuoYZYahong ZhangCWCong Wang

Key Result

Genistein treatment at 50 mg/kg significantly increased the survival rate of EV71-infected neonatal mice from 57.14% to 92.85%.

Key Points

  • This research aims to investigate the antiviral effects of genistein on enterovirus A71 (EV71) and its mechanisms of action.
  • Conducted in vitro assays to evaluate EV71 replication inhibition and mechanistic effects.
  • Performed in vivo experiments using neonatal mice to assess genistein's protective role against EV71.
  • Analyzed the compound's broad-spectrum activity against other enteroviruses like EV68 and CA6.
  • Genistein significantly inhibited EV71 replication, reducing viral genome copies and protein expression.
  • The compound was also effective against EV68 and CA6, showing broad-spectrum antiviral activity.
  • Mechanistically, genistein induced autophagy inhibition and G2/M cell cycle arrest, contributing to its antiviral effects.

Structured PICO

Does genistein reduce EV71 replication and EV71-associated disease in in vitro cell models and neonatal ICR mice?

P
Population
In vitro human rhabdomyosarcoma RD cells, human cervical cancer HeLa cells, and in vivo neonatal ICR mice infected with EV71
I
Intervention
Genistein (in vitro: up to 100 μM; in vivo: 10 mg/kg or 50 mg/kg intraperitoneally once daily for 7 days)
C
Comparator
Vehicle control (in vitro: 10% DMEM with DMSO; in vivo: saline containing 8% DMSO)
O
Outcome
Inhibition of EV71 replication (viral genome copies, viral protein expression, virion numbers) and protection against EV71-associated diseasesurrogate

Genistein demonstrates antiviral activity against enterovirus A71 in vitro and in vivo by modulating autophagy and inducing cell cycle arrest.

Main Result

Absolute Event Rate: 92.85% vs 57.14%

p-value: p=<0.001

Abstract

Background Genistein, an isoflavone abundant in soybeans and other legumes, has shown antiviral activity against several viruses. Its effects on enteroviruses, particularly EV71—the causative agent of hand, foot, and mouth disease (HFMD)—remain incompletely understood. Methods In vitro assays were used to evaluate replication inhibition of EV71, assess mechanistic effects, and determine the compound’s broad-spectrum activity against other enteroviruses (EV68 and CA6). In vivo experiments in neonatal mice were conducted to further elucidate the role of genistein in EV71 replication. Results Genistein inhibited EV71 replication, as evidenced by reduced viral genome copies, decreased viral protein expression, and lower virion numbers. The compound also reduced replication of EV68 and CA6. Mechanistically, autophagy inhibition contributed to the suppression of EV71 replication, and restoring autophagy attenuated this effect. Additionally, genistein caused a G2/M cell cycle arrest, contributing to impaired EV71 replication. In neonatal mice, genistein conferred protection against EV71-associated disease. Conclusion The compound effectively suppresses EV71 replication and mitigates EV71-induced pathology, with concurrent activity against EV68 and CA6, and involves autophagy modulation and cell cycle disruption as part of its antiviral mechanism.

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Cite This Study

Huo et al. (2026) studied Enterovirus A71 (EV71) infection. Genistein vs. Vehicle control (saline containing 8% DMSO) was evaluated on Survival rate of EV71-infected neonatal mice (p=<0.001). Genistein treatment at 50 mg/kg significantly increased the survival rate of EV71-infected neonatal mice from 57.14% to 92.85%.

synapsesocial.com/papers/69e7132bcb99343efc98ce97https://doi.org/10.3389/fphar.2026.1787050
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