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To hit or not to hit: large-scale sequence analysis and structure characterization of influenza A NS1 unlocks new antiviral target potential

2019-04-27Journal article Restricted access
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dc.contributor.authorTrigueiro-Louro, João M.
dc.contributor.authorCorreia, Vanessa
dc.contributor.authorSantos, Luís A.
dc.contributor.authorGuedes, Rita C.
dc.contributor.authorBrito, Rui M.M.
dc.contributor.authorRebelo-de-Andrade, Helena
dc.date.accessioned2020-05-11T09:41:54Z
dc.date.available2020-05-11T09:41:54Z
dc.date.issued2019-04-27
dc.description.abstractInfluenza NS1 protein is among the most promising novel druggable anti-influenza target, based on its structure; multiple interactions; and global function in influenza replication and pathogenesis. Notwithstanding, drug development guidance based on NS1 structural biology is lacking. Here, we design a promising strategy directed to highly conserved druggable regions as a result of an exhaustive large-scale sequence analysis and structure characterization of NS1 protein across human-infecting influenza A subtypes, over the past 100 years. We have identified 3 druggable pockets and 8 new potential hot spot residues in the NS1 protein, not described before, additionally to other 16 sites previously identified, which represent attractive targets for pharmacological modulation. This study provides a rationale towards structure-function studies of NS1 druggable sites, which have the potential to accelerate the NS1 target validation. This research also contributes to a deeper comprehension and insight into the evolutionary dynamics of influenza A NS1 protein.pt_PT
dc.description.abstractHighlights: Anti-influenza strategies based on highly conserved target structures are needed; Overall, the human NS1 protein is highly conserved in the RBD and ED domains; Three main consensus druggable pockets were found with high druggability score; 8 new potential hot spots were identified within the NS1-ED; The study discloses a new panel for NS1 structure-function studies.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationVirology. 2019 Sep;535:297-307. doi: 10.1016/j.virol.2019.04.009. Epub 2019 Apr 27pt_PT
dc.identifier.doi10.1016/j.virol.2019.04.009pt_PT
dc.identifier.issn0042-6822
dc.identifier.urihttp://hdl.handle.net/10400.18/6649
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevier/ Academic Presspt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/abs/pii/S0042682219301096?via%3Dihubpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectAntiviral Agentspt_PT
dc.subjectBinding Sitespt_PT
dc.subjectComputational Biologypt_PT
dc.subjectConserved Sequencept_PT
dc.subjectDrug Developmentpt_PT
dc.subjectHumanspt_PT
dc.subjectInfluenza A viruspt_PT
dc.subjectProtein Bindingpt_PT
dc.subjectProtein Conformationpt_PT
dc.subjectViral Nonstructural Proteinspt_PT
dc.subjectDrug Designpt_PT
dc.subjectResistência aos Antimicrobianospt_PT
dc.subjectInfecções Respiratóriaspt_PT
dc.titleTo hit or not to hit: large-scale sequence analysis and structure characterization of influenza A NS1 unlocks new antiviral target potentialpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage307pt_PT
oaire.citation.startPage297pt_PT
oaire.citation.titleVirologypt_PT
oaire.citation.volume535pt_PT
rcaap.embargofctDe acordo com política editorial da revista.pt_PT
rcaap.rightsembargoedAccesspt_PT
rcaap.typearticlept_PT

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