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dc.contributor.authorButrym, Marta
dc.contributor.authorByvald, Fabian
dc.contributor.authorBlanter, Marfa
dc.contributor.authorRingqvist, Emma E.
dc.contributor.authorVasylovska, Svitlana
dc.contributor.authorMarjomäki, Varpu
dc.contributor.authorLau, Joey
dc.contributor.authorStone, Virginia M.
dc.contributor.authorFlodström-Tullberg, Malin
dc.date.accessioned2024-10-31T10:44:55Z
dc.date.available2024-10-31T10:44:55Z
dc.date.issued2024
dc.identifier.citationButrym, M., Byvald, F., Blanter, M., Ringqvist, E. E., Vasylovska, S., Marjomäki, V., Lau, J., Stone, V. M., & Flodström-Tullberg, M. (2024). Vemurafenib inhibits the replication of diabetogenic enteroviruses in intestinal epithelial and pancreatic beta cells. <i>Antiviral Research</i>, <i>231</i>, Article 106021. <a href="https://doi.org/10.1016/j.antiviral.2024.106021" target="_blank">https://doi.org/10.1016/j.antiviral.2024.106021</a>
dc.identifier.otherCONVID_243577512
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/97921
dc.description.abstractEnteroviruses, which infect via the gut, have been implicated in type 1 diabetes (T1D) development. Prolonged faecal shedding of enterovirus has been associated with islet autoimmunity. Additionally, enteroviral proteins and viral RNA have been detected in the pancreatic islets of individuals with recent-onset T1D, implicating their possible role in beta cell destruction. Despite this, no approved antiviral drugs currently exist that specifically target enterovirus infections for utilisation in disease interventions. Drug repurposing allows for the discovery of new clinical uses for existing drugs and can expedite drug discovery. Previously, the cancer drug Vemurafenib demonstrated unprecedented antiviral activity against several enteroviruses. In the present study, we assessed the efficacy of Vemurafenib and an analogue thereof in preventing infection or reducing the replication of enteroviruses associated with T1D. We tested Vemurafenib in intestinal epithelial cells (IECs) and insulin-producing beta cells. Additionally, we established a protocol for infecting human stem cell-derived islets (SC-islets) and used Vemurafenib and its analogue in this model. Our studies revealed that Vemurafenib exhibited strong antiviral properties in IECs and a beta cell line. The antiviral effect was also seen with the Vemurafenib analogue. SC-islets expressed the viral receptors CAR and DAF, with their highest expression in insulin- and glucagon-positive cells, respectively. SC-islets were successfully infected by CVBs and the antiviral activity of Vemurafenib and its analogue was confirmed in most SC-islet batches. In summary, our observations suggest that Vemurafenib and its analogue warrant further exploration as potential antiviral agents for the treatment of enterovirus-induced diseases, including T1D.en
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofseriesAntiviral Research
dc.rightsCC BY 4.0
dc.subject.otherAntiviral
dc.subject.othercoxsackievirus
dc.subject.otherenterovirus
dc.subject.otherintestinal epithelial cells
dc.subject.otherpancreatic beta cells
dc.subject.othertype 1 diabetes
dc.subject.othervemurafenib
dc.titleVemurafenib inhibits the replication of diabetogenic enteroviruses in intestinal epithelial and pancreatic beta cells
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-202410316771
dc.contributor.laitosBio- ja ympäristötieteiden laitosfi
dc.contributor.laitosDepartment of Biological and Environmental Scienceen
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.type.coarhttp://purl.org/coar/resource_type/c_2df8fbb1
dc.description.reviewstatuspeerReviewed
dc.relation.issn0166-3542
dc.relation.volume231
dc.type.versionpublishedVersion
dc.rights.copyright© 2024 the Authors
dc.rights.accesslevelopenAccessfi
dc.subject.ysoautoimmuunisairaudet
dc.subject.ysoinfektiot
dc.subject.ysonuoruustyypin diabetes
dc.subject.ysolääkesuunnittelu
dc.subject.ysoenterovirukset
dc.subject.ysoepiteelisolut
dc.format.contentfulltext
jyx.subject.urihttp://www.yso.fi/onto/yso/p16178
jyx.subject.urihttp://www.yso.fi/onto/yso/p7316
jyx.subject.urihttp://www.yso.fi/onto/yso/p19788
jyx.subject.urihttp://www.yso.fi/onto/yso/p25180
jyx.subject.urihttp://www.yso.fi/onto/yso/p20689
jyx.subject.urihttp://www.yso.fi/onto/yso/p28973
dc.rights.urlhttps://creativecommons.org/licenses/by/4.0/
dc.relation.doi10.1016/j.antiviral.2024.106021
jyx.fundinginformationThis work was supported by grants from the Swedish Child Diabetes Foundation (M. F-T., V.M.S.), The Swedish Diabetes Foundation (M. F-T.). Karolinska Institutet, Sweden, including the Strategic Research Programme in Diabetes (M. F-T.), National Strategic Research Programmes Excellence of Diabetes Research in Sweden (Exodiab) (J.L.), StemTherapy (J.L.), the Ernfors Family Foundation (J.L.), Jane and Aatos Erkko Foundation (V. M.) and the Swedish Research Council (grant numbers 2020-02969 and 2023-02290; M. F-T.).
dc.type.okmA1


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