A Novel Sphingosine Kinase Inhibitor Suppresses Chikungunya Virus Infection

dc.contributor.authorOyewole, Opeoluwa O.en
dc.contributor.authorDunnavant, Kyleen
dc.contributor.authorBhattarai, Shauraven
dc.contributor.authorKharel, Yugeshen
dc.contributor.authorLynch, Kevin R.en
dc.contributor.authorSantos, Webster L.en
dc.contributor.authorReid, St. Patricken
dc.date.accessioned2022-06-01T19:19:06Zen
dc.date.available2022-06-01T19:19:06Zen
dc.date.issued2022-05-24en
dc.date.updated2022-05-27T13:36:33Zen
dc.description.abstractChikungunya virus (CHIKV) is a re-emerging arbovirus in the alphavirus genus. Upon infection, it can cause severe joint pain that can last years in some patients, significantly affecting their quality of life. Currently, there are no vaccines or anti-viral therapies available against CHIKV. Its spread to the Americas from the eastern continents has substantially increased the count of the infected by millions. Thus, there is an urgent need to identify therapeutic targets for CHIKV treatment. A potential point of intervention is the sphingosine-1-phosphate (S1P) pathway. Conversion of sphingosine to S1P is catalyzed by Sphingosine kinases (SKs), which we previously showed to be crucial pro-viral host factor during CHIKV infection. In this study, we screened inhibitors of SKs and identified a novel potent inhibitor of CHIKV infection&mdash;SLL3071511. We showed that the pre-treatment of cells with SLL3071511 in vitro effectively inhibited CHIKV infection with an EC<sub>50</sub> value of 2.91 &micro;M under both prophylactic and therapeutic modes, significantly decreasing the viral gene expression and release of viral particles. Our studies suggest that targeting SKs is a viable approach for controlling CHIKV replication.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationOyewole, O.O.; Dunnavant, K.; Bhattarai, S.; Kharel, Y.; Lynch, K.R.; Santos, W.L.; Reid, S.P. A Novel Sphingosine Kinase Inhibitor Suppresses Chikungunya Virus Infection. Viruses 2022, 14, 1123.en
dc.identifier.doihttps://doi.org/10.3390/v14061123en
dc.identifier.urihttp://hdl.handle.net/10919/110387en
dc.language.isoenen
dc.publisherMDPIen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectSphingosine kinase 2en
dc.subjectChikungunya virusen
dc.subjectSLL3071511 inhibitoren
dc.subjectantiviralen
dc.subjectdrug discoveryen
dc.titleA Novel Sphingosine Kinase Inhibitor Suppresses Chikungunya Virus Infectionen
dc.title.serialVirusesen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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