Institute of Virology and Antiviral Therapy, Jena University Hospital, Friedrich Schiller University Jena, Hans-Knöll-Str. 2, 07745, Jena, Germany.
Center of Electron Microscopy, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany.
Med Microbiol Immunol. 2015 Dec;204(6):635-45. doi: 10.1007/s00430-015-0391-4. Epub 2015 Feb 14.
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.
药物治疗抑制代谢途径不仅可以降低肥胖引起的人类疾病的风险，还可能阻碍不同病毒病原体的复制。为了研究已获美国食品和药物管理局批准的抗肥胖药物奥利司他的抗病毒活性，针对不同的人致病病毒，我们进行了几项抗病毒研究、电子显微镜分析和脂肪酸摄取实验。结果表明，奥利司他的非细胞毒性浓度给药显著降低了不同细胞类型中柯萨奇病毒 B3（CVB3）的复制。此外，奥利司他还显示出细胞保护作用，并改变了 CVB3 感染细胞中病毒复制所需的多层结构的形成。通过 phloretin 给药降低细胞外环境中的脂肪酸摄取对 CVB3 复制的影响很小。最后，奥利司他也适度减少了水痘带状疱疹病毒的复制，但对甲型流感病毒的复制没有显著影响。这些数据支持进一步研究奥利司他作为脂肪酸合酶抑制剂的价值，以开发基于细胞代谢途径调节的新型抗病毒化合物。
