利用戊型肝炎病毒体外高效培养平台筛选抗HEV药物

戊型肝炎病毒（HEV）感染已成为威胁全球的公共卫生问题。目前还没有有效治疗的药物。临床常用的药物，如利巴韦林和干扰素不能有效清除HEV的复制，并且还会引起强烈的副作用。本项目拟利用前期建立的HEV体外培养平台和HEV感染模型，从细胞和动物模型水平筛选出有效抗HEV的药物。通过从①靶向HEV基因组，②靶向宿主免疫系统或通路，③保肝/护肝三个方面，从携带荧光素酶报告基因的初步筛选，到携带EGFP的HEV感染性克隆，再到活病毒进一步确认，最后利用HEV慢性化感染动物模型和HEV感染孕鼠模型进行药效评价，从而全面、系统地筛选出在体外和体内均能有效清除HEV的候选药物，同时阐明候选药物与HEV的相互作用机制。从靶向病毒本身，到干预宿主免疫系统，再到保护患者肝脏；从体外细胞水平到体内动物模型，层层筛选出有效清除HEV的药物，为深入研究抗HEV药物提供重要基础。

Hepatitis E virus (HEV) infection is an important public health issue. However, no specific drugs for HEV infection in clinical. Ribavirin (RBV) or interferon-α (IFN-α) is off-label drugs. The effect of RBV and IFN-α single or combination treatment is poor response and result in severe side effects. The aim of this study is to efficiently screen anti-HEV drugs in vitro and in vivo by targeting viral genome, host immune system/ pathway, or protecting patients’ liver. Drugs will be screened in cells transfected with HEV-luc expressed plasmid firstly, and then identified in cell transfected with HEV-EGFP infectious cDNA clone, and confirmed in cell infected with HEV. Then, the anti-HEV effects of candidate drugs will further assessed in chronic HEV-infected BALB/c mice and HEV-infected pregnant BALB/c mice. The antiviral mechanism of candidate drugs will also explored. The study is important to develop effective anti-HEV drugs.