Boriskin Y S, Leneva I A, Pécheur E-I, Polyak S J
Institute of Virology, Moscow, Russia.
Curr Med Chem. 2008;15(10):997-1005. doi: 10.2174/092986708784049658.
Arbidol (ARB; ethyl-6-bromo-4-[(dimethylamino)methyl]-5-hydroxy-1-methyl-2-[(phenylthio)methyl]-indole-3-carboxylate hydrochloride monohydrate), is a Russian-made potent broad-spectrum antiviral with demonstrated activity against a number of enveloped and non-enveloped viruses. ARB is well known in Russia and China, although to a lesser extent in western countries. Unlike other broad-spectrum antivirals, ARB has an established molecular mechanism of action against influenza A and B viruses, which is different from that of available influenza antivirals, and a more recently established mechanism of inhibition of hepatitis C virus (HCV). For both viral infections the anti-viral mechanism involves ARB inhibition of virus-mediated fusion with target membrane and a resulting block of virus entry into target cells. However, ARB inhibition of fusion exploits different ARB modalities in case of influenza viruses or HCV. This review aims to summarize the available evidence of ARB effects against different groups of viruses, also, to compare various aspects of ARB anti-fusion mechanisms against influenza virus and HCV (with reference to different stringency of pH-dependence of these two viral fusogens) and to discuss further prospects for ARB and its improved derivatives of the parent compounds.
阿比朵尔(ARB;盐酸盐一水合物,即6-溴-4-[(二甲氨基)甲基]-5-羟基-1-甲基-2-[(苯硫基)甲基]吲哚-3-羧酸乙酯)是一种俄罗斯制造的强效广谱抗病毒药物,已证明对多种包膜病毒和非包膜病毒具有活性。ARB在俄罗斯和中国广为人知,不过在西方国家的知名度相对较低。与其他广谱抗病毒药物不同,ARB对甲型和乙型流感病毒具有既定的分子作用机制,这与现有的流感抗病毒药物不同,并且最近还确立了其抑制丙型肝炎病毒(HCV)的机制。对于这两种病毒感染,抗病毒机制都涉及ARB抑制病毒介导的与靶膜融合以及由此导致的病毒进入靶细胞受阻。然而,在流感病毒或HCV的情况下,ARB对融合的抑制利用了不同的ARB作用方式。本综述旨在总结ARB对不同病毒组作用的现有证据,同时比较ARB针对流感病毒和HCV的抗融合机制的各个方面(参考这两种病毒融合蛋白对pH依赖性的不同严格程度),并讨论ARB及其母体化合物改进衍生物的进一步前景。