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dc.contributor.authorPatel, Hershna
dc.contributor.authorKukol, Andreas
dc.date.accessioned2019-10-02T00:20:38Z
dc.date.available2019-10-02T00:20:38Z
dc.date.issued2019-11-01
dc.identifier.citationPatel , H & Kukol , A 2019 , ' Prediction of ligands to universally conserved binding sites of the influenza A virus nuclear export protein ' , Virology , vol. 537 , pp. 97-103 . https://doi.org/10.1016/j.virol.2019.08.013
dc.identifier.issn0042-6822
dc.identifier.otherPURE: 17445471
dc.identifier.otherPURE UUID: be9917c6-91ee-43f1-9867-e24f245d9b6d
dc.identifier.otherScopus: 85072290591
dc.identifier.urihttp://hdl.handle.net/2299/21714
dc.description© 2019 Elsevier Inc. All rights reserved.
dc.description.abstractThe nuclear export protein (NEP) of the influenza A virus exports viral ribonucleoproteins to the host cell cytoplasm following nuclear transcription. In this work conservation analysis of 3000 protein sequences and molecular modelling of full-length NEP identified ligand binding sites overlapping with high sequence conservation. Two binding hot spots were identified close to the first nuclear export signal and several hot spots overlapped with highly conserved amino acids such as Arg42, Asp43, Lys39, Ile80, Gln101 and Val109. Virtual screening with ~43,000 compounds against a binding site showed affinities of up to −8.95 kcal/mol, while ~1700 approved drugs showed affinities of up to −8.31 kcal/mol. A drug-like compounds predicted was ZINC01564229 that could be used as probe to investigate NEP function or as a new drug lead. The approved drugs Nandrolone phenylpropionate and Estropipate were predicted to bind with high affinity and may be investigated for repurposing as anti-influenza drugs. Importance: The influenza A virus causes respiratory illness in humans and farm animals annually across the world. Antigenic shifts and drifts in the surface proteins lead to genome diversity and unpredictable pandemics and epidemics. The high evolution rate of the RNA genome can also limit the effectiveness of antivirals and is the cause of emerging resistance. From a human health perspective, it is important that compounds identified as potential influenza replication inhibitors remain effective long-term. This work presents results which are based on computational predictions that reveal interactions between available compounds and regions of the influenza A nuclear export protein which display high conservation. Due to a low probability of highly conserved regions undergoing genomic changes, these compounds may serve as ideal leads for new antivirals.en
dc.format.extent7
dc.language.isoeng
dc.relation.ispartofVirology
dc.subjectInfluenza A
dc.subjectnuclear export protein
dc.subjectsequence conservation
dc.subjectbinding site
dc.subjectvirtual screening
dc.subjectvirus
dc.subjectSequence conservation
dc.subjectVirtual screening
dc.subjectInfluenza a
dc.subjectBinding site
dc.subjectNuclear export protein
dc.subjectVirology
dc.titlePrediction of ligands to universally conserved binding sites of the influenza A virus nuclear export proteinen
dc.contributor.institutionDepartment of Biological and Environmental Sciences
dc.contributor.institutionAgriculture, Veterinary and Food Sciences
dc.contributor.institutionBiosciences Research Group
dc.contributor.institutionSchool of Life and Medical Sciences
dc.description.statusPeer reviewed
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85072290591&partnerID=8YFLogxK
rioxxterms.versionAM
rioxxterms.versionofrecordhttps://doi.org/10.1016/j.virol.2019.08.013
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


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