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Proc Natl Acad Sci U S A. 2013 Apr 2;110(14):5463-7. doi: 10.1073/pnas.1222379110. Epub 2013 Mar 18.

Structure of human enterovirus 71 in complex with a capsid-binding inhibitor.

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  • 1Department of Biological Sciences, Purdue University, West Lafayette, IN 47907-2032, USA.

Abstract

Human enterovirus 71 is a picornavirus causing hand, foot, and mouth disease that may progress to fatal encephalitis in infants and small children. As of now, no cure is available for enterovirus 71 infections. Small molecule inhibitors binding into a hydrophobic pocket within capsid viral protein 1 were previously shown to effectively limit infectivity of many picornaviruses. Here we report a 3.2-Å-resolution X-ray structure of the enterovirus 71 virion complexed with the capsid-binding inhibitor WIN 51711. The inhibitor replaced the natural pocket factor within the viral protein 1 pocket without inducing any detectable rearrangements in the structure of the capsid. Furthermore, we show that the compound stabilizes enterovirus 71 virions and limits its infectivity, probably through restricting dynamics of the capsid necessary for genome release. Thus, our results provide a structural basis for development of antienterovirus 71 capsid-binding drugs.

PMID:
23509286
[PubMed - indexed for MEDLINE]
PMCID:
PMC3619292
Free PMC Article
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