Structure and inhibition of EV-D68, a virus that causes respiratory illness in children

Science. 2015 Jan 2;347(6217):71-4. doi: 10.1126/science.1261962.

Abstract

Enterovirus D68 (EV-D68) is a member of Picornaviridae and is a causative agent of recent outbreaks of respiratory illness in children in the United States. We report here the crystal structures of EV-D68 and its complex with pleconaril, a capsid-binding compound that had been developed as an anti-rhinovirus drug. The hydrophobic drug-binding pocket in viral protein 1 contained density that is consistent with a fatty acid of about 10 carbon atoms. This density could be displaced by pleconaril. We also showed that pleconaril inhibits EV-D68 at a half-maximal effective concentration of 430 nanomolar and might, therefore, be a possible drug candidate to alleviate EV-D68 outbreaks.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Capsid / chemistry*
  • Capsid / drug effects
  • Capsid / ultrastructure
  • Child
  • Crystallography, X-Ray
  • Enterovirus D, Human / chemistry*
  • Enterovirus D, Human / drug effects
  • Enterovirus D, Human / ultrastructure
  • Enterovirus Infections / drug therapy
  • Enterovirus Infections / epidemiology
  • Enterovirus Infections / virology*
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Oxadiazoles / chemistry*
  • Oxadiazoles / pharmacology
  • Oxadiazoles / therapeutic use
  • Oxazoles
  • Respiratory Tract Diseases / drug therapy
  • Respiratory Tract Diseases / epidemiology
  • Respiratory Tract Diseases / virology*
  • United States / epidemiology
  • Viral Proteins / chemistry
  • Viral Proteins / ultrastructure

Substances

  • Antiviral Agents
  • Oxadiazoles
  • Oxazoles
  • Viral Proteins
  • pleconaril

Associated data

  • PDB/4WM7
  • PDB/4WM8