乙型肝炎病毒（HBV）感染可引起急性和慢性肝炎，部分可演变为肝纤维化、肝硬化、肝癌和肝功能衰竭。慢性乙型肝炎是我国最严重的慢性传染性疾病之一，目前尚无法治愈，因此迫切需要新型抗乙肝药物的研发。体外抗HBV药物筛选过程中，我们发现CDDO和CDDO-EA具有抗HBV活性；前期实验结果提示药物可影响HBV前基因组RNA（pgRNA）被包裹进入衣壳的相关过程。文献报道CDDO类化合物主要靶点是Nrf2，Nrf2激活剂在多种肝脏疾病中起到保护作用。本课题将以CDDO-EA为代表，拟在多个细胞模型上明确其抗HBV药效；进一步在HBV持续感染小鼠模型上评价其体内抗HBV药效；以Nrf2通路和影响pgRNA衣壳化的相关因素为线索，系统阐明CDDO-EA抗HBV的机制。本课题将为Nrf2能否成为抗HBV靶点和CDDO-EA能否成为抗HBV先导物奠定理论基础，也为后续新型抗HBV药物研发提供科学数据。

Hepatitis B virus（HBV）infection causes acute and chronic hepatitis, which will evolve into various server liver diseases, including fibrosis, cirrhosis, hepatocellular carcinoma (HCC) and liver failure. Then chronic hepatitis is one of the most serious chronic infectious diseases in China and it can’t be cured yet. In the effort toward screening and discovery of novel antiviral agents against HBV, we found that CDDO and CDDO-EA can significantly inhibit HBV replication. Furthermore, we found that the compounds can affect the process of viral pgRNA encapsidation. It has been reported that CDDO and its derivatives show biological activity by inducing Nrf2 activation, which can protect liver from injury of various diseases. In this project, we will take CDDO-EA as the representative to confirm the antiviral efficacy on several cell models, evaluate the antiviral activity in a HBV-mediated chronic hepatitis mouse model and then systematically explore the antiviral mechanisms based on the Nrf2 pathway and the related factors affecting the pgRNA encapsidation. Our study will provide theoretical basis for whether Nrf2 can become a target for developing anti-HBV drug and whether CDDO-EA can become a lead compound against HBV. It will also provide scientific data for further development of novel antiviral agents against HBV.