Huang Zhuhui, Murray Michael G, Secrist John A
Southern Research Institute, 431 Aviation Way, Frederick, MD 21701, USA.
Antiviral Res. 2006 Sep;71(2-3):351-62. doi: 10.1016/j.antiviral.2006.06.001. Epub 2006 Jun 23.
The global prevalence of hepatitis C virus (HCV) infection and serious health consequences associated with chronic state of the disease have become a significant health problem worldwide. Currently, there is no vaccine to prevent the disease and no specific antiviral drug directed against HCV infection. The current standard of care, interferon-based therapies, both alone or in combination with ribavirin, has demonstrated limited success and is associated with undesirable side effects. Thus, the treatment of the chronic HCV infection represents an unmet medical need. With advances in the understanding of HCV replication and the crystal structures of the virally encoded enzymes, the HCV NS3/4A serine protease and the NS5B RNA-dependent RNA polymerase have emerged as ideal targets toward the control of the disease and the development of new anti-HCV agents. In this review, we will summarize the current treatment options, and outline the approaches toward discovery of small molecule antivirals against the virally encoded enzymes. The current clinical studies of promising lead compounds are also reviewed.
丙型肝炎病毒(HCV)感染的全球流行率以及与该疾病慢性状态相关的严重健康后果已成为全球重大的健康问题。目前,尚无预防该疾病的疫苗,也没有针对HCV感染的特异性抗病毒药物。当前的护理标准,即基于干扰素的疗法,无论是单独使用还是与利巴韦林联合使用,都已证明效果有限且伴有不良副作用。因此,慢性HCV感染的治疗仍是未满足的医疗需求。随着对HCV复制以及病毒编码酶晶体结构认识的进展,HCV NS3/4A丝氨酸蛋白酶和NS5B RNA依赖性RNA聚合酶已成为控制该疾病和开发新型抗HCV药物的理想靶点。在本综述中,我们将总结当前的治疗选择,并概述针对病毒编码酶发现小分子抗病毒药物的方法。还将对有前景的先导化合物的当前临床研究进行综述。