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Here, we show that compounds interfering with intracellular cholesterol transport have the capacity to inhibit CHIKV replication in human skin fibroblasts, a major viral entry site in the human host. Pretreatment of these cells with the class II cationic amphiphilic compound U18666A, or treatment with the FDA-approved antidepressant drug imipramine resulted in a near total inhibition of viral replication and production at the highest concentration used without any cytotoxic effects. Imipramine was found to affect both the fusion and replication steps of the viral life cycle. The key contribution of cholesterol availability to the CHIKV life cycle was validated further by the use of fibroblasts from Niemann-Pick type C (NPC) patients in which the virus was unable to replicate. Interestingly, imipramine also strongly inhibited the replication of several <jats:italic>Flaviviridae<\/jats:italic> family members, including Zika, West Nile and Dengue virus. Together, these data show that this compound is a potential drug candidate for anti-arboviral treatment.<\/jats:p>","DOI":"10.1038\/s41598-017-03316-5","type":"journal-article","created":{"date-parts":[[2017,6,5]],"date-time":"2017-06-05T09:29:39Z","timestamp":1496654979000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":100,"title":["Imipramine Inhibits Chikungunya Virus Replication in Human Skin Fibroblasts through Interference with Intracellular Cholesterol Trafficking"],"prefix":"10.1038","volume":"7","author":[{"given":"Sineewanlaya","family":"Wichit","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodolphe","family":"Hamel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Bernard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lo\u00efc","family":"Talignani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fod\u00e9","family":"Diop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Ferraris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1048-0661","authenticated-orcid":false,"given":"Florian","family":"Liegeois","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peeraya","family":"Ekchariyawat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natthanej","family":"Luplertlop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pornapat","family":"Surasombatpattana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Merits","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Choumet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1825-1054","authenticated-orcid":false,"given":"Pierre","family":"Roques","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Yssel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Briant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doroth\u00e9e","family":"Miss\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,6,9]]},"reference":[{"key":"3316_CR1","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.1086\/517537","volume":"44","author":"G Borgherini","year":"2007","unstructured":"Borgherini, G. et al. Outbreak of chikungunya on Reunion Island: early clinical and laboratory features in 157 adult patients. Clin Infect Dis \n                           44, 1401\u20131407 (2007).","journal-title":"Clin Infect Dis"},{"key":"3316_CR2","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/j.antiviral.2013.06.009","volume":"99","author":"SD Thiberville","year":"2013","unstructured":"Thiberville, S. D. et al. Chikungunya fever: epidemiology, clinical syndrome, pathogenesis and therapy. Antiviral Res \n                           99, 345\u2013370 (2013).","journal-title":"Antiviral Res"},{"key":"3316_CR3","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/0035-9203(55)90080-8","volume":"49","author":"MC ROBINSON","year":"1955","unstructured":"ROBINSON, M. C. An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952\u201353. I. Clinical features. 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