Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 14, Pages 5463-5467Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1222379110
Keywords
stability; virus
Categories
Funding
- National Institutes of Health, National Center for Research Resources (NIH/NCRR) [RR007707]
- US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]
- NIH/NCRR [RR025761]
- NIH [AI11219]
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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-angstrom-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.
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