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dc.contributor.authorDirr, Larissa
dc.contributor.authorEl-Deeb, Ibrahim M
dc.contributor.authorChavas, Leonard MG
dc.contributor.authorGuillon, Patrice
dc.contributor.authorvon Itzstein, Mark
dc.date.accessioned2017-09-22T04:57:10Z
dc.date.available2017-09-22T04:57:10Z
dc.date.issued2017
dc.identifier.issn2045-2322
dc.identifier.doi10.1038/s41598-017-04656-y
dc.identifier.urihttp://hdl.handle.net/10072/347167
dc.description.abstractHuman parainfluenza viruses represent a leading cause of lower respiratory tract disease in children, with currently no available approved drug or vaccine. The viral surface glycoprotein haemagglutinin-neuraminidase (HN) represents an ideal antiviral target. Herein, we describe the first structure-based study on the rearrangement of key active site amino acid residues by an induced opening of the 216-loop, through the accommodation of appropriately functionalised neuraminic acid-based inhibitors. We discovered that the rearrangement is influenced by the degree of loop opening and is controlled by the neuraminic acid’s C-4 substituent’s size (large or small). In this study, we found that these rearrangements induce a butterfly effect of paramount importance in HN inhibitor design and define criteria for the ideal substituent size in two different categories of HN inhibitors and provide novel structural insight into the druggable viral HN protein.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherNature Publishing Group
dc.relation.ispartofpagefrom4507-1
dc.relation.ispartofpageto4507-10
dc.relation.ispartofjournalScientific Reports
dc.relation.ispartofvolume7
dc.subject.fieldofresearchBiochemistry and Cell Biology not elsewhere classified
dc.subject.fieldofresearchcode060199
dc.titleThe impact of the butterfly effect on human parainfluenza virus haemagglutinin-neuraminidase inhibitor design
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.description.versionPublished
gro.facultyOffice of the Snr Dep Vice Chancellor, Institute for Glycomics
gro.rights.copyright© The Author(s) Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
gro.hasfulltextFull Text
gro.griffith.authorvon Itzstein, Mark
gro.griffith.authorGuillon, Patrice M.
gro.griffith.authorEl-Deeb, Ibrahim Mustafa
gro.griffith.authorDirr, Larissa E.


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