Recent advance in antiviral drugs for hepatitis C.
Recent advance in antiviral drugs for hepatitis C.
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DOI：
10.3969/j.issn.1672-7347.2011.11.001
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发表时间：
2011-11-01
期刊：
影响因子：
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通讯作者：
Luo, Guangxiang
中科院分区：
文献类型：
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作者：
Liu, Jia;Shi, Shuang;Luo, Guangxiang
丙型肝炎病毒（HCV）感染是全世界慢性肝病的主要原因。没有疫苗可以预防丙型肝炎病毒感染。目前丙型肝炎的护理标准 (SOC) 是聚乙二醇干扰素-α (pegIFN-α) 联合利巴韦林 (RBV)。然而，pegIFN-α和RBV联合治疗对于人类主要病毒基因1型HCV的疗效不足50%。此外，IFN和RBV具有剧毒，会引起严重的副作用。因此，开发更安全、更有效的抗HCV药物刻不容缓。在过去的十年中，已经发现了许多 HCV 特异性抑制剂，其中许多已进入临床试验的后期阶段。近日，2种HCV NS3蛋白酶抑制剂特拉匹韦和波普匹韦已获得美国食品药品监督管理局（FDA）批准。这开启了抗HCV治疗的新时代。针对 HCV NS3 蛋白酶、NS5A 和 NS5B RNA 依赖性 RNA 聚合酶 (RdRp) 的几类新型抗病毒药物目前正处于临床前和临床研究的不同阶段。随着更多 NS3 蛋白酶、NS5A 和 NS5B 聚合酶抑制剂获得批准，未来的临床研究将产生最佳的联合疗法，该疗法将具有无干扰素、更高疗效、安全、每日一剂和短疗程等理想参数。
Hepatitis C virus (HCV) infection is the leading cause of chronic liver diseases worldwide. There is no vaccine to prevent HCV infection. Current standard of care (SOC) for hepatitis C is pegylated interferon-alpha (pegIFN-alpha) in combination with ribavirin (RBV). However, the efficacy of pegIFN-alpha and RBV combination therapy is less than 50% for genotype 1 HCV, which is the dominant virus in human. Additionally, IFN and RBV are highly toxic, causing severe side effects. Therefore, it is urgent to develop safer and more efficacious anti-HCV drugs. Over the last decade, a number of HCV-specific inhibitors have been discovered with many of them reached to late stages of clinical trials. Recently, 2 HCV NS3 protease inhibitors, telaprevir and boceprevir, have been approved by the Unite States Food and Drug Administration (FDA). This opens up a new era for anti-HCV therapy. Several new classes of antiviral drugs targeting HCV NS3 protease, NS5A and NS5B RNA-dependence RNA polymerase (RdRp) are currently at various stages of preclinical and clinical studies. Upon approval of more NS3 protease, NS5A and NS5B polymerase inhibitors, future clinical studies will lead to optimal combination therapies which will have desirable parameters such as IFN-free, higher efficacy, safe, one daily dose and short duration.