title: The anti-obesity drug orlistat reveals anti-viral activity.
abstract: The administration of drugs to inhibit metabolic pathways not only reduces the risk of obesity-induced diseases in humans but may also hamper the replication of different viral pathogens. In order to investigate the value of the US Food and Drug Administration-approved anti-obesity drug orlistat in view of its anti-viral activity against different human-pathogenic viruses, several anti-viral studies, electron microscopy analyses as well as fatty acid uptake experiments were performed. The results indicate that administrations of non-cytotoxic concentrations of orlistat reduced the replication of coxsackievirus B3 (CVB3) in different cell types significantly. Moreover, orlistat revealed cell protective effects and modified the formation of multi-layered structures in CVB3-infected cells, which are necessary for viral replication. Lowering fatty acid uptake from the extracellular environment by phloretin administrations had only marginal impact on CVB3 replication. Finally, orlistat reduced also the replication of varicella-zoster virus moderately but had no significant influence on the replication of influenza A viruses. The data support further experiments into the value of orlistat as an inhibitor of the fatty acid synthase to develop new anti-viral compounds, which are based on the modulation of cellular metabolic pathways.
authors: Institute of Virology and Antiviral Therapy, Jena University Hospital, Friedrich Schiller University Jena, Hans-Knöll-Str. 2, 07745, Jena, Germany.
authors: Elisabeth
authors: E
authors: Ammer
authors: Center of Electron Microscopy, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany.
authors: Sandor
authors: S
authors: Nietzsche
authors: Institute of Virology and Antiviral Therapy, Jena University Hospital, Friedrich Schiller University Jena, Hans-Knöll-Str. 2, 07745, Jena, Germany.
authors: Christian
authors: C
authors: Rien
authors: Institute of Virology and Antiviral Therapy, Jena University Hospital, Friedrich Schiller University Jena, Hans-Knöll-Str. 2, 07745, Jena, Germany.
authors: Alexander
authors: A
authors: Kühnl
authors: Institute of Virology and Antiviral Therapy, Jena University Hospital, Friedrich Schiller University Jena, Hans-Knöll-Str. 2, 07745, Jena, Germany.
authors: Theresa
authors: T
authors: Mader
authors: Institute for Molecular Cell Biology, Center for Molecular Biomedicine, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany.
authors: Regine
authors: R
authors: Heller
authors: Institute of Virology and Antiviral Therapy, Jena University Hospital, Friedrich Schiller University Jena, Hans-Knöll-Str. 2, 07745, Jena, Germany.
authors: Andreas
authors: A
authors: Sauerbrei
authors: Institute of Virology and Antiviral Therapy, Jena University Hospital, Friedrich Schiller University Jena, Hans-Knöll-Str. 2, 07745, Jena, Germany. Andreas.Henke@med.uni-jena.de.
authors: Andreas
authors: A
authors: Henke
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D029822:Enterovirus B, Human / Q000187:drug effects; D014645:Herpesvirus 3, Human / Q000187:drug effects; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects; D007783:Lactones / Q000494:pharmacology*; D000077403:Orlistat; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019440:Anti-Obesity Agents; D000998:Antiviral Agents; D007783:Lactones; D000077403:Orlistat
keywords: Anti-viral activity; Coxsackievirus B3; Electron microscopy; Fatty acid synthase; Influenza A virus; Orlistat; Varicella-zoster virus