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Inhibition of enterovirus 71 replication by chrysosplenetin and penduletin

Qin-Chang Zhu1, Yi Wang, Ya-Ping Liu

  • 1State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
|September 15, 2011
PubMed

Insights

Chrysosplenetin and penduletin show potent antiviral activity against enterovirus 71 (EV71) by inhibiting viral RNA replication. These natural compounds offer a promising avenue for developing new treatments for EV71 infections in children.

Area of Science:

  • Natural Product Chemistry
  • Virology
  • Drug Discovery

Background:

  • Enterovirus 71 (EV71) infections pose a significant threat to young children, causing severe neurological disease and mortality.
  • Current therapeutic options for EV71 are limited, highlighting the urgent need for novel antiviral agents.

Purpose of the Study:

  • To investigate the anti-EV71 activity of chrysosplenetin and penduletin, two o-methylated flavonols from Laggera pterodonta.
  • To evaluate the efficacy and preliminary mechanism of action of these compounds against EV71.

Main Methods:

  • In vitro antiviral activity assessed using cytopathic effect (CPE) inhibition assays, including plaque reduction and virus yield inhibition.
  • Cytotoxicity evaluated in African green monkey kidney (Vero) and human rhabdomyosarcoma (RD) cells to determine selectivity indices (SI).
  • Mechanism of action explored through time-of-addition assays and assessment of viral RNA replication inhibition.

Main Results:

  • Chrysosplenetin and penduletin demonstrated strong in vitro activity against EV71 with low cytotoxicity, exhibiting 50% inhibitory concentration (IC50) values around 0.20 μM.
  • High selectivity indices (SI) were observed in both Vero (107.5–655.6) and RD (69.5–200.5) cells.
  • Compounds were found to inhibit viral RNA replication, not virus entry or direct inactivation, with optimal efficacy when administered within 4 hours post-infection.
  • Activity was also observed against other human enteroviruses.

Conclusions:

  • Chrysosplenetin and penduletin are effective inhibitors of EV71 replication, acting by suppressing viral RNA synthesis.
  • These flavonols exhibit favorable safety profiles and broad-spectrum activity against enteroviruses.
  • The findings present chrysosplenetin and penduletin as promising candidates for the development of novel anti-EV71 therapeutics.

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