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dc.contributor.authorEveno, Tanguy
dc.contributor.authorDirr, Larissa
dc.contributor.authorEl-Deeb, Ibrahim M
dc.contributor.authorGuillon, Patrice
dc.contributor.authorvon Itzstein, Mark
dc.date.accessioned2019-07-15T02:57:03Z
dc.date.available2019-07-15T02:57:03Z
dc.date.issued2019
dc.identifier.issn1999-4915
dc.identifier.doi10.3390/v11050417
dc.identifier.urihttp://hdl.handle.net/10072/386393
dc.description.abstractHuman parainfluenza virus (hPIV) infections are a major cause of respiratory tract illnesses in children, with currently no available vaccine or drug treatment. The surface glycoprotein haemagglutinin-neuraminidase (HN) of hPIV has a central role in the viral life cycle, including neuraminic acid-recognising receptor binding activity (early stage) and receptor-destroying activity (late stage), which makes it an ideal target for antiviral drug disovery. In this study, we showed that targeting the catalytic mechanism of hPIV-1 HN by a 2α,3β-difluoro derivative of the known hPIV-1 inhibitor, BCX 2798, produced more potent inhibition of the neuraminidase function which is reflected by a stronger inhibition of viral replication. The difluorosialic acid-based inhibitor efficiently blocked the neuraminidase activity of HN for a prolonged period of time relative to its unsaturated neuraminic acid (Neu2en) analogue, BCX 2798 and produced a more efficient inhibition of the HN neuraminidase activity as well as in vitro viral replication. This prolonged inhibition of the hPIV-1 HN protein suggests covalent binding of the inhibitor to a key catalytic amino acid, making this compound a new lead for a novel class of more potent hPIV-1 mechanism-based inhibitors.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI)
dc.relation.ispartofpagefrom1
dc.relation.ispartofpageto10
dc.relation.ispartofissue5
dc.relation.ispartofjournalViruses
dc.relation.ispartofvolume11
dc.subject.fieldofresearchMicrobiology
dc.subject.fieldofresearchcode3107
dc.titleTargeting human parainfluenza virus type-1 haemagglutinin-neuraminidase with mechanism-based inhibitors
dc.typeJournal article
dc.type.descriptionC2 - Articles (Other)
dc.type.codeC - Journal Articles
dcterms.licensehttps://creativecommons.org/licenses/by/4.0/
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2019 The Authors. This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
gro.hasfulltextFull Text
gro.griffith.authorvon Itzstein, Mark
gro.griffith.authorGuillon, Patrice M.
gro.griffith.authorDirr, Larissa E.
gro.griffith.authorEl-Deeb, Ibrahim Mustafa


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