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基于病毒和宿主因素的潜在抗乙型肝炎病毒药物靶点

Potential Drug Targets Against Hepatitis B Virus Based on Both Virus and Host Factors.

作者信息

Zhang Bing-Yi, Chai Dan-Ping, Wu Yi-Hang, Qiu Li-Peng, Zhang Yong-Yong, Ye Zi-Hong, Yu Xiao-Ping

机构信息

Department of Pharmacy, Zhejiang Provincial Key Laboratory of Biometrology and Inspection & Quarantine, College of Life Sciences, China Jiliang University, Hangzhou 310018, China.

Institute of Life Sciences, Jiangsu University, Zhenjiang 212013, China.

出版信息

Curr Drug Targets. 2019;20(16):1636-1651. doi: 10.2174/1389450120666190729115646.

Abstract

BACKGROUND

Hepatitis B is a very harmful and epidemic disease caused by hepatitis B virus (HBV). Although an effective anti-HBV vaccine is available, chronic infection poses still a huge health burden in the whole world. The present anti-HBV drugs including nucleoside analogues and interferonalpha have their limitations without exception. There is no effective drug and therapeutic method that can really and truly cure hepatitis B so far. The variability of HBV genome results in that a significant number of patients develop drug resistance during the long-term use of anti-HBV drugs. Hence, it is urgently needed to discover novel targets and develop new drugs against hepatitis B.

OBJECTIVE

The review aims to provide the theory support for designing of the anti-HBV innovative drugs by offering a summary of the current situation of antiviral potential targets.

RESULTS AND CONCLUSION

Since HBV is obligate intracellular parasite, and as such it depends on host cellular components and functions to replicate itself. The targeting both virus and host might be a novel therapeutic option for hepatitis B. Accordingly, we analyse the advances in the study of the potential drug targets for anti-HBV infection, focusing on targeting virus genome, on targeting host cellular functions and on targeting virus-host proteins interactions, respectively. Meanwhile, the immune targets against chronic hepatitis B are also emphasized. In short, the review provides a summary of antiviral therapeutic strategies to target virus factors, host factors and immune factors for future designing of the innovative drug against HBV infection.

摘要

背景

乙型肝炎是由乙型肝炎病毒(HBV)引起的一种极具危害性的流行性疾病。尽管有有效的抗HBV疫苗,但慢性感染在全球范围内仍然构成巨大的健康负担。目前的抗HBV药物,包括核苷类似物和α干扰素,无一例外都有其局限性。迄今为止,尚无真正能治愈乙型肝炎的有效药物和治疗方法。HBV基因组的变异性导致大量患者在长期使用抗HBV药物过程中产生耐药性。因此,迫切需要发现新的靶点并开发抗乙型肝炎的新药。

目的

通过综述抗病毒潜在靶点的研究现状,为抗HBV创新药物的设计提供理论支持。

结果与结论

由于HBV是专性细胞内寄生虫,因此它依赖宿主细胞成分和功能进行自身复制。针对病毒和宿主的双重靶向可能是治疗乙型肝炎的一种新策略。据此,我们分别从靶向病毒基因组、靶向宿主细胞功能以及靶向病毒-宿主蛋白相互作用三个方面分析了抗HBV感染潜在药物靶点的研究进展。同时,也强调了针对慢性乙型肝炎的免疫靶点。总之,本综述总结了针对病毒因子、宿主因子和免疫因子的抗病毒治疗策略,为未来设计抗HBV感染的创新药物提供参考。

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