Show simple item record

dc.contributor.authorPatel, Hershna
dc.contributor.authorKukol, Andreas
dc.date.accessioned2017-09-01T15:17:37Z
dc.date.available2017-09-01T15:17:37Z
dc.date.issued2017-09-01
dc.identifier.citationPatel , H & Kukol , A 2017 , ' Evolutionary conservation of influenza A PB2 sequences reveals potential target sites for small molecule inhibitors ' , Virology , vol. 509 , pp. 112-120 . https://doi.org/10.1016/j.virol.2017.06.009
dc.identifier.issn0042-6822
dc.identifier.urihttp://hdl.handle.net/2299/19286
dc.descriptionThis document is the Accepted Manuscript version of the following article: Hershna Patel and Andreas Kukol, 'Evolutionary conservation of influenza A PB2 sequences reveals potential target sites for small molecule inhibitors', Virology, Vol. 509, pp. 112-120, June 2017. The version of record is available online at doi: https://doi.org/10.1016/j.virol.2017.06.009. © 2017 Published by Elsevier Inc.
dc.description.abstractThe influenza A basic polymerase protein 2 (PB2) functions as part of a heterotrimer to replicate the viral RNA genome. To investigate novel PB2 antiviral target sites, this work identified evolutionary conserved regions across the PB2 protein sequence amongst all sub-types and hosts, as well as ligand binding hot spots which overlap with highly conserved areas. Fifteen binding sites were predicted in different PB2 domains; some of which reside in areas of unknown function. Virtual screening of ~50,000 drug-like compounds showed binding affinities of up to 10.3 kcal/mol. The highest affinity molecules were found to interact with conserved residues including Gln138, Gly222, Ile529, Asn540 and Thr530. A library containing 1738 FDA approved drugs were screened additionally and revealed Paliperidone as a top hit with a binding affinity of -10 kcal/mol. Predicted ligands are ideal leads for new antivirals as they were targeted to evolutionary conserved binding sites.en
dc.format.extent9
dc.format.extent1794123
dc.language.isoeng
dc.relation.ispartofVirology
dc.titleEvolutionary conservation of influenza A PB2 sequences reveals potential target sites for small molecule inhibitorsen
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionBiosciences Research Group
dc.contributor.institutionCentre for Research in Mechanisms of Disease and Drug Discovery
dc.contributor.institutionDepartment of Clinical, Pharmaceutical and Biological Science
dc.contributor.institutionCentre for Future Societies Research
dc.description.statusPeer reviewed
dc.date.embargoedUntil2018-06-17
rioxxterms.versionofrecord10.1016/j.virol.2017.06.009
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record