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

Pavel Plevka, Rushika Perera, Moh Lan Yap, Jane Cardosa, Richard J Kuhn, Michael G Rossmann

Proceedings of the National Academy of Sciences of the United States of America 2013 Apr 02

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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-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.

Citation

Pavel Plevka, Rushika Perera, Moh Lan Yap, Jane Cardosa, Richard J Kuhn, Michael G Rossmann. Structure of human enterovirus 71 in complex with a capsid-binding inhibitor. Proceedings of the National Academy of Sciences of the United States of America. 2013 Apr 02;110(14):5463-7