title: Inhibition of fatty acid synthase by amentoflavone reduces coxsackievirus B3 replication.
abstract: Coxsackievirus B3 (CVB3) is a human pathogen that causes acute and chronic infections, but an antiviral drug to treat these diseases has not yet been developed for clinical use. Several intracellular pathways are altered to assist viral transcription, RNA replication, and progeny release. Among these, fatty acid synthase (FAS) expression is increased. In order to test the potential of FAS inhibition as an anti-CVB3 strategy, several experiments were performed, including studies on the correlation of CVB3 replication and FAS expression in human Raji cells and an analysis of the time and dose dependence of the antiviral effect of FAS inhibition due to treatment with amentoflavone. The results demonstrate that CVB3 infection induces an up-regulation of FAS expression already at 1 h postinfection (p.i.). Incubation with increasing concentrations of amentoflavone inhibited CVB3 replication significantly up to 8 h p.i. In addition, suppression of p38 MAP kinase activity by treatment with SB239063 decreased FAS expression as well as viral replication. These data provide evidence that FAS inhibition via amentoflavone administration might present a target for anti-CVB3 therapy.
authors.affiliation: Department of Virology and Antiviral Therapy, University Hospital Jena, Friedrich Schiller University, Hans-Knöll-Str. 2, 07745 Jena, Germany.
authors.forename: Steffi
authors.initials: S
authors.lastname: Wilsky
authors.forename: Katharina
authors.initials: K
authors.lastname: Sobotta
authors.forename: Nadine
authors.initials: N
authors.lastname: Wiesener
authors.forename: Johanna
authors.initials: J
authors.lastname: Pilas
authors.forename: Nadine
authors.initials: N
authors.lastname: Althof
authors.forename: Thomas
authors.initials: T
authors.lastname: Munder
authors.forename: Peter
authors.initials: P
authors.lastname: Wutzler
authors.forename: Andreas
authors.initials: A
authors.lastname: Henke
mesh_terms: D044946:Biflavonoids / Q000494:pharmacology*; D002460:Cell Line; D003384:Coxsackievirus Infections / Q000188:drug therapy / Q000201:enzymology* / Q000821:virology; D015536:Down-Regulation / Q000187:drug effects*; D029822:Enterovirus B, Human / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015854:Up-Regulation / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D044946:Biflavonoids; D004791:Enzyme Inhibitors; C011164:amentoflavone; D064429:Fatty Acid Synthases