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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Imipramine Inhibits Chikungunya Virus Replication in Human Skin Fibroblasts through Interference with Intracellular Cholesterol Trafficking
Scientific Reports, Volume 7, No. 1, Article 3145, Year 2017
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Description
Chikungunya virus (CHIKV) is an emerging arbovirus of the Togaviridae family that poses a present worldwide threat to human in the absence of any licensed vaccine or antiviral treatment to control viral infection. 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 Flaviviridae 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. © 2017 The Author(s).
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC5466638/bin/41598_2017_3316_MOESM1_ESM.pdf
Authors & Co-Authors
Wichit, Sineewanlaya
France, Montpellier
Université de Montpellier
Hamel, Rodolphe
France, Montpellier
Université de Montpellier
Talignani, Loïc
France, Montpellier
Université de Montpellier
Diop, Fodé
France, Montpellier
Université de Montpellier
Ferraris, Pauline
France, Montpellier
Université de Montpellier
Liégeois, Florian
France, Montpellier
Université de Montpellier
Thomas, Frédéric
France, Montpellier
Université de Montpellier
Merits, Andres
Estonia, Tartu
Tartu Ülikool
Choumet, Valérie
France, Paris
Institut Pasteur, Paris
Roques, Pierre A.
France, Gif-sur-yvette
Institut Des Maladies Emergentes et Des Thérapies Innovantes
France, Fontenay-aux-roses
Immunologie Des Maladies Virales, Auto-immunes, Hematologiques et Bacteriennes
Yssel, Hans
France, Paris
Sorbonne Université
Missé, Dorothée A.
France, Montpellier
Université de Montpellier
Statistics
Citations: 73
Authors: 12
Affiliations: 9
Identifiers
Doi:
10.1038/s41598-017-03316-5
ISSN:
20452322
Research Areas
Infectious Diseases