Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Department of Infectious Diseases, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Molecules. 2022 Aug 6;27(15):5000. doi: 10.3390/molecules27155000.
HBx plays a significant role in the cccDNA epigenetic modification regulating the hepatitis B virus (HBV) life cycle and in hepatocyte proliferation and carcinogenesis. By using the sleeping-beauty transposon system, we constructed a tetracycline-induced HBx-expressing stable cell line, SBHX21. HBx with a HiBiT tag can be quickly detected utilizing a NanoLuc-based HiBiT detection system. By screening a drug library using SBHX21 cells, we identified estradiol benzoate as a novel anti-HBx agent. Estradiol benzoate also markedly reduced the production of HBeAg, HBsAg, HBV pgRNA, and HBV DNA in a dose-dependent manner, suggesting that estradiol benzoate could be an anti-HBV agent. Docking model results revealed that estradiol benzoate binds to HBx at TRP87 and TRP107. Collectively, our results suggest that estradiol benzoate inhibits the HBx protein and HBV transcription and replication, which may serve as a novel anti-HBV molecular compound for investigating new treatment strategies for HBV infection.
HBx 在调节乙型肝炎病毒 (HBV) 生命周期和肝细胞增殖及癌变的 cccDNA 表观遗传修饰中发挥重要作用。我们利用睡眠美人转座子系统构建了一个四环素诱导表达 HBx 的稳定细胞系 SBHX21。带有 HiBiT 标签的 HBx 可利用基于 NanoLuc 的 HiBiT 检测系统快速检测。通过用 SBHX21 细胞筛选药物文库，我们发现苯甲酸雌二醇是一种新型抗 HBx 药物。苯甲酸雌二醇还能显著降低 HBeAg、HBsAg、HBV pgRNA 和 HBV DNA 的产生，呈剂量依赖性，提示苯甲酸雌二醇可能是一种抗 HBV 药物。对接模型结果表明，苯甲酸雌二醇结合到 HBx 的 TRP87 和 TRP107 上。综上，我们的结果表明苯甲酸雌二醇抑制 HBx 蛋白和 HBV 转录和复制，可能成为一种新的抗 HBV 分子化合物，用于研究 HBV 感染的新治疗策略。
