University of Illinois at Chicago, Department of Medicine, Chicago, IL 60612, USA.
Expert Opin Drug Discov. 2012 Sep;7(9):849-59. doi: 10.1517/17460441.2012.711312. Epub 2012 Aug 4.
Hepatitis C virus (HCV) is a major cause of liver disease worldwide and the leading indication for liver transplantation in the United States. Current treatment options are expensive, not effective in all patients and are associated with serious side effects. Although preclinical, anti-HCV drug screening is still hampered by the lack of readily infectable small animal models, the development of cell culture HCV experimental model systems has driven a promising new wave of HCV antiviral drug discovery.
This review contains a concise overview of current HCV treatment options and limitations with a subsequent in-depth focus on the available experimental models and novel strategies that have, and continue to enable, important advances in HCV drug development.
With a large cohort of chronically HCV-infected patients progressively developing liver disease that puts them at risk for hepatocellular carcinoma and hepatic decompensation, there is an urgent need to develop effective therapeutics that are well tolerated and effective in all patients and against all HCV genotypes. Significant advances in HCV experimental model development have expedited drug discovery; however, additional progress is needed. Importantly, the current trends and momentum in the field suggests that we will continue to overcome critical experimental challenges to reach this end goal.
丙型肝炎病毒(HCV)是全球范围内导致肝脏疾病的主要原因,也是美国肝移植的主要指征。目前的治疗选择昂贵,并非对所有患者都有效,并且存在严重的副作用。尽管处于临床前阶段,但抗 HCV 药物筛选仍然受到缺乏易于感染的小动物模型的阻碍,细胞培养 HCV 实验模型系统的发展推动了 HCV 抗病毒药物发现的新一波浪潮。
本文简要概述了目前 HCV 的治疗选择和局限性,随后深入探讨了现有的实验模型和新策略,这些模型和策略在 HCV 药物开发方面取得了重要进展。
随着大量慢性 HCV 感染患者逐渐发展为肝脏疾病,使他们面临肝细胞癌和肝功能失代偿的风险,迫切需要开发出有效、耐受性好且对所有患者和所有 HCV 基因型均有效的治疗方法。HCV 实验模型开发的重大进展加速了药物发现;然而,还需要进一步的进展。重要的是,目前该领域的趋势和动力表明,我们将继续克服关键的实验挑战,实现这一最终目标。