dc.contributor.author | Butrym, Marta | |
dc.contributor.author | Byvald, Fabian | |
dc.contributor.author | Blanter, Marfa | |
dc.contributor.author | Ringqvist, Emma E. | |
dc.contributor.author | Vasylovska, Svitlana | |
dc.contributor.author | Marjomäki, Varpu | |
dc.contributor.author | Lau, Joey | |
dc.contributor.author | Stone, Virginia M. | |
dc.contributor.author | Flodström-Tullberg, Malin | |
dc.date.accessioned | 2024-10-31T10:44:55Z | |
dc.date.available | 2024-10-31T10:44:55Z | |
dc.date.issued | 2024 | |
dc.identifier.citation | Butrym, 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.other | CONVID_243577512 | |
dc.identifier.uri | https://jyx.jyu.fi/handle/123456789/97921 | |
dc.description.abstract | Enteroviruses, 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.mimetype | application/pdf | |
dc.language.iso | eng | |
dc.publisher | Elsevier | |
dc.relation.ispartofseries | Antiviral Research | |
dc.rights | CC BY 4.0 | |
dc.subject.other | Antiviral | |
dc.subject.other | coxsackievirus | |
dc.subject.other | enterovirus | |
dc.subject.other | intestinal epithelial cells | |
dc.subject.other | pancreatic beta cells | |
dc.subject.other | type 1 diabetes | |
dc.subject.other | vemurafenib | |
dc.title | Vemurafenib inhibits the replication of diabetogenic enteroviruses in intestinal epithelial and pancreatic beta cells | |
dc.type | research article | |
dc.identifier.urn | URN:NBN:fi:jyu-202410316771 | |
dc.contributor.laitos | Bio- ja ympäristötieteiden laitos | fi |
dc.contributor.laitos | Department of Biological and Environmental Science | en |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | |
dc.type.coar | http://purl.org/coar/resource_type/c_2df8fbb1 | |
dc.description.reviewstatus | peerReviewed | |
dc.relation.issn | 0166-3542 | |
dc.relation.volume | 231 | |
dc.type.version | publishedVersion | |
dc.rights.copyright | © 2024 the Authors | |
dc.rights.accesslevel | openAccess | fi |
dc.type.publication | article | |
dc.subject.yso | autoimmuunisairaudet | |
dc.subject.yso | infektiot | |
dc.subject.yso | nuoruustyypin diabetes | |
dc.subject.yso | lääkesuunnittelu | |
dc.subject.yso | enterovirukset | |
dc.subject.yso | epiteelisolut | |
dc.format.content | fulltext | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p16178 | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p7316 | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p19788 | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p25180 | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p20689 | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p28973 | |
dc.rights.url | https://creativecommons.org/licenses/by/4.0/ | |
dc.relation.doi | 10.1016/j.antiviral.2024.106021 | |
jyx.fundinginformation | This 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.okm | A1 | |