钾离子通道介导蝎毒素多肽Hp98抑制HBV复制研究

慢性乙型肝炎病毒感染是造成慢性肝炎、肝硬化以及肝癌的重要病因，已严重威胁人类的健康。尽管临床有治疗药物如核苷类似物和干扰素等，但有易于产生耐药等不良反应，有必要发现新的抗HBV物质并阐述其作用靶标与分子机制。我们前期研究发现彼得异蝎的毒素多肽Hp98不仅抑制HBV的复制，而且调节钾离子通道的活性。本项目在现有工作基础上，拟开展4方面的研究工作：1)蝎毒素多肽Hp98体外抑制HBV复制；2)蝎毒素多肽Hp98体内抗HBV效应；3) 蝎毒素多肽Hp98抑制HBV复制和调节钾离子通道的关系；4) 钾离子通道介导蝎毒素多肽Hp98抑制HBV复制的分子机制，最终阐明钾离子通道介导Hp98多肽抑制HBV复制效应及其新机制，为科学利用我国蝎毒素多肽资源、发现抗HBV新先导多肽和药物靶标奠定基础。

Chronic hepatitis B virus (HBV) infection causes liver disease and is a main health problem worldwide. Although therapeutical nucleotide analogs, and interferons were used for HBV-infected people, they are easy to produce drug resistance and adverse reactions, resulting in the increased number of HBV-related death. Thus, there is a vital need for the development of new therapy agents or candidate sources involved in novel anti-HBV mechanisms. Recently, we isolated and characterized a new peptide Hp98 from the venom of the scorpion Heterometrus petersii. Hp98 peptide not only inhibits the replication of HBV at the cellular level in a dose-dependent manner, but also modulates the activity of potassium channel on the cellular membranes. In this project, we will perform the following four contents focusing on the anti-HBV activity and mechanism of the peptide Hp98: 1) Anti-HBV activity of scorpion venom peptide Hp98 in vitro; 2) Effect of scorpion venom peptide Hp98 on HBV in vivo; 3) The relationship between anti-HBV and modulating-channel activities of scorpion venom peptide Hp98; 4) Clarification of the anti-HBV cell signal transduction pathway of the peptide Hp98 mediated by ion channels. All these works will be in the service for exploiting scorpion venom peptide, discovering anti-HBV drug lead peptides and targets.