诱导乙肝病毒核壳体异常组装机制的研究

In recent years, potential new targets, aside from HBV polymerase, have been explored and include viral RNA transcription factors, capsid formation, and envelope protein modification.We found that a seris of non-nucleoside anti-HBV active compounds can induce the formation of abnormal vacuolated HBV nucleocapsid without viral nucleic acid, which is different from the reported mechanisms of anti-HBV compounds. To use the combination research techniques of viral molecular biology related, the project intends to use a novel non-nucleoside anti-HBV compounds as the tool to clarify the mechanism of the formation of abnormal nucleocapsid, elucidate the mechanism of capsid assembly of HBV and its impact on viral cccDNA generation, and establish the new target for anti-HBV drugs. These results will provide the scientific and research basis for the discovery and development of new drugs targeting viral capsid assembly of HBV and other related virus.

针对上市核苷类抗HBV药物作用靶点单一的问题，新型抗HBV药物的研究已有较大进展，尤其是干扰HBV核壳体组装的抗HBV活性化合物在近年相继出现。我们研发的非核苷类小分子抗HBV活性化合物能够诱导不含病毒核酸、空泡状HBV异常核壳体的形成，已确认与被报道的干扰核壳体组装的活性化合物作用机制不同。本研究将运用自主发现的新型抗HBV活性化合物作为研究工具药，结合病毒分子生物学研究技术，研究诱导不含病毒核酸、异常核壳体的形成机制，阐明HBV核壳体组装的分子机制、深入解析病毒核壳体组装的调节过程以及药物对病毒cccDNA的影响作用、发现药物抑制HBV复制作用位点，确证抗HBV药物作用新靶点，为研制抗HBV核壳体组装药物的研究提供扎实的科学依据。