Sebastian Liba, Desai Anita, Madhusudana Shampur Narayan, Ravi Vasanthapuram
Department of Neurovirology, National Institute of Mental Health and Neurosciences, Bangalore, India.
Int J Antimicrob Agents. 2009 Feb;33(2):168-73. doi: 10.1016/j.ijantimicag.2008.07.013. Epub 2008 Sep 18.
Several investigations have shown that pentoxifylline possesses broad-spectrum antiviral activity against a range of RNA and DNA viruses. However, its ability to inhibit Japanese encephalitis virus (JEV) replication has not yet been studied. The present study was designed to investigate the antiviral activity of pentoxifylline against JEV in vitro and in vivo. The activity of pentoxifylline against JEV was evaluated in vitro using cytopathic effect inhibition and plaque reduction assays. Pentoxifylline was able to inhibit JEV replication in a dose-dependent manner at a 50% inhibitory concentration (IC(50)) of 50.3microg/mL (0.00018microM) and a therapeutic index (TI) of 10. Experiments to study the mechanism of antiviral action of pentoxifylline using in vitro translation of viral mRNA suggested that the drug did not interfere either with early or late protein synthesis but most likely exerted its action on virus assembly and/or release. Furthermore, the in vivo study showed that pentoxifylline at a concentration of 100mg/kg and 200mg/kg body weight was able to protect completely mice challenged with 50 x 50% lethal dose (LD(50)) of JEV.
多项研究表明，己酮可可碱对多种RNA和DNA病毒具有广谱抗病毒活性。然而，其抑制日本脑炎病毒（JEV）复制的能力尚未得到研究。本研究旨在调查己酮可可碱在体外和体内对JEV的抗病毒活性。使用细胞病变效应抑制和蚀斑减少试验在体外评估己酮可可碱对JEV的活性。己酮可可碱能够以剂量依赖方式抑制JEV复制，其50%抑制浓度（IC50）为50.3μg/mL（0.00018μM），治疗指数（TI）为10。利用病毒mRNA体外翻译研究己酮可可碱抗病毒作用机制的实验表明，该药物既不干扰早期也不干扰晚期蛋白质合成，但很可能对病毒组装和/或释放发挥作用。此外，体内研究表明，体重100mg/kg和200mg/kg的己酮可可碱能够完全保护受到50×50%致死剂量（LD50）JEV攻击的小鼠。
