dc.contributor.author | Patel, Hershna | |
dc.contributor.author | Kukol, Andreas | |
dc.date.accessioned | 2017-09-01T15:17:37Z | |
dc.date.available | 2017-09-01T15:17:37Z | |
dc.date.issued | 2017-09-01 | |
dc.identifier.citation | Patel , 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.issn | 0042-6822 | |
dc.identifier.uri | http://hdl.handle.net/2299/19286 | |
dc.description | This 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.abstract | The 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.extent | 9 | |
dc.format.extent | 1794123 | |
dc.language.iso | eng | |
dc.relation.ispartof | Virology | |
dc.title | Evolutionary conservation of influenza A PB2 sequences reveals potential target sites for small molecule inhibitors | en |
dc.contributor.institution | School of Life and Medical Sciences | |
dc.contributor.institution | Biosciences Research Group | |
dc.contributor.institution | Centre for Research in Mechanisms of Disease and Drug Discovery | |
dc.contributor.institution | Department of Clinical, Pharmaceutical and Biological Science | |
dc.contributor.institution | Centre for Future Societies Research | |
dc.description.status | Peer reviewed | |
dc.date.embargoedUntil | 2018-06-17 | |
rioxxterms.versionofrecord | 10.1016/j.virol.2017.06.009 | |
rioxxterms.type | Journal Article/Review | |
herts.preservation.rarelyaccessed | true | |