PD169316, a specific p38 inhibitor, shows antiviral activity against Enterovirus71

Virology. 2017 Aug:508:150-158. doi: 10.1016/j.virol.2017.05.012. Epub 2017 May 22.

Abstract

Enterovirus71 (EV71) is the major causative agent of hand, foot and mouth disease, which threatens the health of infants and young children. The expression of inflammatory cytokines induced by this viral infection aggravate the illness. Here, we describe the anti-EV71 activity of a specific p38 inhibitor that regulates the p38-MAPK signaling pathway. PD169316 was specifically selected from a MAPK compound library due to its significant inhibitory effect on EV71 replication. PD169316 also reduced EV71-induced apoptosis. Animal experiments showed that PD169316 can dampen the replication of EV71, reduce tissue damage and inhibit the release of inflammatory cytokines, thereby alleviating the severe diseases caused by EV71 in suckling mice.

Keywords: Antiviral therapy; EV71; PD169316; p38-MAPK.

MeSH terms

  • Animals
  • Antiviral Agents / administration & dosage*
  • Apoptosis
  • Enterovirus A, Human / drug effects*
  • Enterovirus A, Human / physiology
  • Enterovirus Infections / drug therapy
  • Enterovirus Infections / physiopathology
  • Enterovirus Infections / virology*
  • Enzyme Inhibitors / administration & dosage*
  • Female
  • Humans
  • Imidazoles / administration & dosage*
  • Male
  • Mice
  • Virus Replication / drug effects
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • Imidazoles
  • p38 Mitogen-Activated Protein Kinases
  • 2-(4-nitrophenyl)-4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazole