摘要
HCV传染病的目前治疗由批准的抗病毒药物(DAAs)构成,也就是蛋白酶抑制剂(波西普韦,替拉瑞韦和simeprevir),NS5B聚合酶抑制剂(sofosbuvir)和NS5A抑制剂(ledipasvir),与聚乙二醇化干扰素α和利巴韦林相结合。近几年,这些治疗在治疗慢性HCV感染方面取得了很大进步,但是他们的副作用、抗药突变体的出现、高成本及增加的药物负担已经局限了他们的临床应用。近期,随着对HCV生命周期了解知识的增加,更多的靶点被认知。NS5A蛋白在集合传染性的HCA颗粒和为HCV治疗提供潜力起到了关键作用。因此,为了提高现存HCV治疗质量,NS5A为靶点的拥有新作用机制的新颖DAAs制剂的发现和开发非常必要。在此综述中,我们讨论了有潜在抗HCV活性的NS5A抑制剂的研究进展,以及抗HCV感染的HCV NS5A抑制剂发展的潜力。
关键词: 抗病毒药,药物设计,丙型肝炎病毒,抑制剂,NS5A
Current Medicinal Chemistry
Title:The Changing Face of Hepatitis C: Recent Advances on HCV Inhibitors Targeting NS5A
Volume: 22 Issue: 15
Author(s): Diwakar Rai, Liu Wang, Xuemei Jiang, Peng Zhan, Haiyong Jia, Erik De Clercq and Xinyong Liu
Affiliation:
关键词: 抗病毒药,药物设计,丙型肝炎病毒,抑制剂,NS5A
摘要: Current treatment for HCV infections consists of approved direct acting antivirals (DAAs), viz. the protease inhibitors (boceprevir, telaprevir, and simeprevir), NS5B polymerase inhibitors (sofosbuvir) and NS5A inhibitor (ledipasvir) in combination with pegylated interferon α and ribavirin). These treatments have made a great improvement in the treatment of chronic HCV infections in recent years, but their adverse side effects, emergence of resistant mutants, high cost, and increased pill burden have limited their clinical use. Recently, with the increasing knowledge in understanding the HCV life cycle, more targets have been recognized. NS5A protein plays a critical role in assembly of infectious HCV particles and offering potential for HCV therapies. Therefore, discovery and development of novel DAAs targeting NS5A with novel mechanisms of action, are of great necessity to improve the quality of existing HCV treatments. In the present review, we discuss recent advances with NS5A inhibitors with potent anti-HCV activity, and the potential for the development of HCV NS5A inhibitors to combat HCV infections.
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Diwakar Rai, Liu Wang, Xuemei Jiang, Peng Zhan, Haiyong Jia, Erik De Clercq and Xinyong Liu , The Changing Face of Hepatitis C: Recent Advances on HCV Inhibitors Targeting NS5A, Current Medicinal Chemistry 2015; 22 (15) . https://dx.doi.org/10.2174/0929867322666150209150920
DOI https://dx.doi.org/10.2174/0929867322666150209150920 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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