title: Structure and inhibition of EV-D68, a virus that causes respiratory illness in children.
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.
authors.affiliation: Department of Biological Sciences, Hockmeyer Hall of Structural Biology, 240 South Martin Jischke Drive, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biological Sciences, Hockmeyer Hall of Structural Biology, 240 South Martin Jischke Drive, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Ju
authors.initials: J
authors.lastname: Sheng
authors.affiliation: Department of Biological Sciences, Hockmeyer Hall of Structural Biology, 240 South Martin Jischke Drive, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Andrei
authors.initials: A
authors.lastname: Fokine
authors.affiliation: Department of Biological Sciences, Hockmeyer Hall of Structural Biology, 240 South Martin Jischke Drive, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Geng
authors.initials: G
authors.lastname: Meng
authors.affiliation: Department of Biological Sciences, Hockmeyer Hall of Structural Biology, 240 South Martin Jischke Drive, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Woong-Hee
authors.initials: WH
authors.lastname: Shin
authors.affiliation: Department of Biological Sciences, Hockmeyer Hall of Structural Biology, 240 South Martin Jischke Drive, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Long
authors.affiliation: Department of Biological Sciences, Hockmeyer Hall of Structural Biology, 240 South Martin Jischke Drive, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kuhn
authors.affiliation: Department of Biological Sciences, Hockmeyer Hall of Structural Biology, 240 South Martin Jischke Drive, Purdue University, West Lafayette, IN 47907, USA. Department of Computer Science, 305 North University Street, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kihara
authors.affiliation: Department of Biological Sciences, Hockmeyer Hall of Structural Biology, 240 South Martin Jischke Drive, Purdue University, West Lafayette, IN 47907, USA. mr@purdue.edu.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rossmann
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D002213:Capsid / Q000737:chemistry* / Q000187:drug effects / Q000648:ultrastructure; D002648:Child; D018360:Crystallography, X-Ray; D030016:Enterovirus D, Human / Q000737:chemistry* / Q000187:drug effects / Q000648:ultrastructure; D004769:Enterovirus Infections / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D010069:Oxadiazoles / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D010080:Oxazoles; D012140:Respiratory Tract Diseases / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology*; D014481:United States / Q000453:epidemiology; D014764:Viral Proteins / Q000737:chemistry / Q000648:ultrastructure
chemical_list: D000998:Antiviral Agents; D010069:Oxadiazoles; D010080:Oxazoles; D014764:Viral Proteins; C115201:pleconaril