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dc.contributor.authorChen, Shun
dc.contributor.authorYang, Chao
dc.contributor.authorZhang, Wei
dc.contributor.authorMahalingam, Suresh
dc.contributor.authorWang, Mingshu
dc.contributor.authorCheng, Anchun
dc.date.accessioned2019-06-19T13:10:42Z
dc.date.available2019-06-19T13:10:42Z
dc.date.issued2018
dc.identifier.issn0163-7258
dc.identifier.doi10.1016/j.pharmthera.2018.05.004
dc.identifier.urihttp://hdl.handle.net/10072/385001
dc.description.abstractInfections with viruses in the Flaviviridae family have a vast global and economic impact because of the high morbidity and mortality. The pathogenesis of Flaviviridae infections is very complex and not fully understood because these viruses can inhibit multiple immune pathways including the complement system, NK cells, and IFN induction and signalling pathways. The non-structural (NS) 5 and 5A proteins of Flaviviridae viruses are highly conserved and play an important role in resisting host immunity through various evasion mechanisms. This review summarizes the strategies used by the NS5 and 5A proteins of Flaviviridae viruses for evading the innate immune response by inhibiting pattern recognition receptor (PRR) signalling pathways (TLR/MyD88, IRF7), suppressing interferon (IFN) signalling pathways (IFN-γRs, STAT1, STAT2), and impairing the function of IFN-stimulated genes (ISGs) (e.g. protein kinase R [PKR], oligoadenylate synthase [OAS]). All of these immune evasion mechanisms depend on the interaction of NS5 or NS5A with cellular proteins, such as MyD88 and IRF7, IFN-αRs, IFN-γRs, STAT1, STAT2, PKR and OAS. NS5 is the most attractive target for the discovery of broad spectrum compounds against Flaviviridae virus infection. The methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) activities of NS5 are the main therapeutic targets for antiviral drugs against Flaviviridae virus infection. Based on our site mapping, the sites involved in immune evasion provide some potential and promising targets for further novel antiviral therapeutics.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier Inc
dc.publisherElsevier
dc.publisher.placeUnited States
dc.relation.ispartofpagefrom1
dc.relation.ispartofpageto14
dc.relation.ispartofjournalPharmacology & Therapeutics
dc.relation.ispartofvolume190
dc.subject.fieldofresearchPharmacology and Pharmaceutical Sciences not elsewhere classified
dc.subject.fieldofresearchPharmacology and Pharmaceutical Sciences
dc.subject.fieldofresearchcode111599
dc.subject.fieldofresearchcode1115
dc.titleFlaviviridae virus nonstructural proteins 5 and 5A mediate viral immune evasion and are promising targets in drug development
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.description.versionAccepted Manuscript (AM)
gro.rights.copyright© 2018 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence, which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorMahalingam, Suresh


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