Caspase-3 inhibitor inhibits enterovirus D68 production

J Microbiol. 2020 Sep;58(9):812-820. doi: 10.1007/s12275-020-0241-y. Epub 2020 Sep 1.


Enterovirus D68 (EVD68) is an emerging pathogen that recently caused a large worldwide outbreak of severe respiratory disease in children. However, the relationship between EVD68 and host cells remains unclear. Caspases are involved in cell death, immune response, and even viral production. We found that caspase-3 was activated during EVD68 replication to induce apoptosis. Caspase-3 inhibitor (Z-DEVD-FMK) inhibited viral production, protected host cells from the cytopathic effects of EVD68 infection, and prevented EVD68 from regulating the host cell cycle at G0/G1. Meanwhile, caspase-3 activator (PAC-1) increased EVD68 production. EVD68 infection therefore activates caspase-3 for virus production. This knowledge provides a potential direction for the prevention and treatment of disease related to EVD68.

Keywords: EVD68; apoptosis; caspase-3; host-pathogen interaction; viral production.

MeSH terms

  • Antiviral Agents / pharmacology*
  • Apoptosis / physiology
  • Caspase 3 / drug effects*
  • Caspase 3 / metabolism*
  • Cell Line, Tumor
  • Enterovirus D, Human / drug effects*
  • Enterovirus D, Human / growth & development*
  • Enterovirus Infections / pathology
  • Enterovirus Infections / prevention & control
  • Enterovirus Infections / virology
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • Hydrazones / pharmacology
  • Oligopeptides / pharmacology
  • Piperazines / pharmacology


  • (4-benzylpiperazin-1-yl)acetic acid (3-allyl-2-hydroxybenzylidene)hydrazine
  • Antiviral Agents
  • Hydrazones
  • Oligopeptides
  • Piperazines
  • benzyloxycarbonyl-aspartyl(OMe)-isoleucyl-prolyl-aspartyl(OMe) fluoromethylketone
  • CASP3 protein, human
  • Caspase 3