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Human enterovirus 71 in complex with capsid binding inhibitor WIN51711Human enterovirus 71 in complex with capsid binding inhibitor WIN51711
Structural highlights
Function[A9X4C2_9ENTO] Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity).[SAAS:SAAS000199_004_016611] Protein 3C is a cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind co-operatively to the protease (By similarity).[SAAS:SAAS000199_004_042266] RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).[SAAS:SAAS000199_004_010047] Publication Abstract from PubMedHuman 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-A-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. Structure of human enterovirus 71 in complex with a capsid-binding inhibitor.,Plevka P, Perera R, Yap ML, Cardosa J, Kuhn RJ, Rossmann MG Proc Natl Acad Sci U S A. 2013 Apr 2;110(14):5463-7. doi:, 10.1073/pnas.1222379110. Epub 2013 Mar 18. PMID:23509286[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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