Ebselen inhibits enterovirus A71-induced apoptosis through reactive oxygen species-mediated signaling pathway

Mol Biol Rep. 2023 Apr;50(4):2991-3000. doi: 10.1007/s11033-022-08116-3. Epub 2023 Jan 18.

Abstract

Background: Enterovirus A71 (EV-A71)is a prevalent infection in severe hand, foot and mouth disease HFMD and can induce acute central nervous system seizures. The three EV-A71 vaccines now circulating in the market are produced for a single subtype. While EV-A71 is constantly evolving and the vaccine's efficacy is gradually reducing, no specialized anti-EV-A71 medication has yet been developed. Therefore, it is crucial to consistently develop new anti-EV-A71 medications.

Method: Ebselen, an organoselenium molecule with glutathione oxidase-like activity, is resistant to a range of viruses. In this investigation, we used the Cell counting kit-8 (CCK-8 kit) assay in a Vero cell model to confirm the effectiveness of ebselen against EV-A71 infection. Later, to examine ebselen's anti-EV-A71 mechanism, we measured the apoptosis level of cells in different treatment groups through Annexin V, JC-1, and cell cycle assays, as well as the intracellular reactive oxygen species (ROS) concentration. Ebselen may have an impact on the apoptotic signaling pathway caused by EV-A71 infection, according to the results of a caspase-3 activity experiment.

Result: The results showed that Ebselen protected cell damage from ROS generation, decreased the frequency of EV-A71-induced apoptosis, and inhibited caspase-3-mediated apoptosis by lowering caspase-3 activity.

Conclusion: To summarize, ebselen is a promising anti-EV-A71 medication.

Keywords: Apoptosis; Caspase-3; EV-A71; Ebselen; ROS.

MeSH terms

  • Apoptosis
  • Caspase 3
  • Enterovirus A, Human*
  • Enterovirus Infections* / drug therapy
  • Enterovirus*
  • Humans
  • Reactive Oxygen Species
  • Signal Transduction

Substances

  • Reactive Oxygen Species
  • Caspase 3
  • ebselen