Gerold Gisa, Pietschmann Thomas
TWINCORE - Centre for Experimental and Clinical Infection Research, Institute of Experimental Virology, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.
Curr Hepat Rep. 2013;12(4):200-213. doi: 10.1007/s11901-013-0187-1. Epub 2013 Oct 4.
Hepatitis C virus (HCV) infects more than 2 % of the world population with highest prevalence in parts of Africa and Asia. Past standard of care using interferon α and ribavirin had adverse effects and showed modest efficacy for some HCV genotypes spurring the development of direct acting antivirals (DAAs). Such DAAs target viral proteins and are thus better tolerated but they suffer from emergence of vial resistance. Furthermore, DAAs are often HCV genotype specific. Novel drug candidates targeting host factors required for HCV propagation, so called host-targeting antivirals (HTAs), promise to overcome both caveats. The genetic barrier to resistance is usually considered to be high for HTAs and all HCV genotypes presumably use the same host factors. Recent data, however, challenge these assumptions, at least for some HTAs. Here, we highlight the most important host-targeting strategies against hepatitis C and critically discuss their opportunities and risks.
丙型肝炎病毒(HCV)感染了全球超过2%的人口,在非洲和亚洲部分地区的流行率最高。过去使用干扰素α和利巴韦林的标准治疗方法有不良反应,并且对某些HCV基因型的疗效一般,这促使了直接作用抗病毒药物(DAA)的研发。这类DAA靶向病毒蛋白,因此耐受性更好,但它们存在病毒耐药性出现的问题。此外,DAA通常具有HCV基因型特异性。针对HCV传播所需宿主因子的新型候选药物,即所谓的宿主靶向抗病毒药物(HTA),有望克服这两个问题。通常认为HTA的耐药遗传屏障较高,并且所有HCV基因型可能使用相同的宿主因子。然而,最近的数据对这些假设提出了挑战,至少对某些HTA是如此。在这里,我们重点介绍针对丙型肝炎最重要的宿主靶向策略,并批判性地讨论它们的机遇和风险。