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dc.contributor.authorKerry, Philip S.
dc.contributor.authorMohan, Sankar
dc.contributor.authorRussell, Rupert J. M.
dc.contributor.authorBance, Nicole
dc.contributor.authorNiikura, Masahiro
dc.contributor.authorPinto, B. Mario
dc.date.accessioned2014-07-10T10:31:02Z
dc.date.available2014-07-10T10:31:02Z
dc.date.issued2013-10-16
dc.identifier.citationKerry , P S , Mohan , S , Russell , R J M , Bance , N , Niikura , M & Pinto , B M 2013 , ' Structural basis for a class of nanomolar influenza A neuraminidase inhibitors ' , Scientific Reports , vol. 3 , e2871 . https://doi.org/10.1038/srep02871en
dc.identifier.issn2045-2322
dc.identifier.otherPURE: 131076303
dc.identifier.otherPURE UUID: 3adb27e3-8e29-45a7-bf76-2b4d95154824
dc.identifier.otherWOS: 000325700400001
dc.identifier.otherScopus: 84893254796
dc.identifier.urihttp://hdl.handle.net/10023/5003
dc.descriptionThe authors thank the Natural Sciences and Engineering Research Council of Canada, the University of St Andrews, and the Scottish Funding Council for financial support.en
dc.description.abstractThe influenza virus neuraminidase (NA) is essential for the virus life cycle. The rise of resistance mutations against current antiviral therapies has increased the need for the development of novel inhibitors. Recent efforts have targeted a cavity adjacent to the catalytic site (the 150-cavity) in addition to the primary catalytic subsite in order to increase specificity and reduce the likelihood of resistance. This study details structural and in vitro analyses of a class of inhibitors that bind uniquely in both subsites. Crystal structures of three inhibitors show occupation of the 150-cavity in two distinct and novel binding modes. We believe these are the first nanomolar inhibitors of NA to be characterized in this way. Furthermore, we show that one inhibitor, binding within the catalytic site, offers reduced susceptibility to known resistance mutations via increased flexibility of a pendant pentyloxy group and the ability to pivot about a strong hydrogen-bonding network.
dc.format.extent6
dc.language.isoeng
dc.relation.ispartofScientific Reportsen
dc.rightsThis work is licensed under a Creative Commons Attribution 3.0 Unported license. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0en
dc.subjectCrystal-structuresen
dc.subjectVirus-activitiesen
dc.subjectActive-siteen
dc.subjectIn-vitroen
dc.subjectOseltamiviren
dc.subjectSialidaseen
dc.subject150-loopen
dc.subjectReplicationen
dc.subjectDerivativesen
dc.subject150-cavityen
dc.subjectQR355 Virologyen
dc.subject.lccQR355en
dc.titleStructural basis for a class of nanomolar influenza A neuraminidase inhibitorsen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.identifier.doihttps://doi.org/10.1038/srep02871
dc.description.statusPeer revieweden


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