Hepatitis B virus (HBV) is the causative agent of chronic liver disease and is correlated with the development of subsequent hepatic cirrhosis and hepatocellular carcinoma. Current antiviral therapy using nucleos(t)ide analogs is effective in suppressing viral replication and interrupting disease progression, but HBV is rarely cured completely. Thus, there remains an unmet need for the development of novel anti-HBV drugs. Here, we report the identification of N-(4-Nitrophenyl)-1-phenylethanone hydrazone (ANPH) as a novel structural class of selective inhibitors targeting the replication of the HBV genome using adenovirus vector-mediated HBV genome transduction. ANPH inhibited viral genome replication in HepG2.2.15 cells by inducing the formation of empty capsids devoid of pregenomic RNA without affecting its transcription and translation. Biochemical assays using a truncated core protein consisting of the assembly domain showed that ANPH accelerates the formation of morphologically intact capsids. Taken together, we propose that ANPH might provide a new structural scaffold to design a new anti-HBV drug in medicinal chemistry as well as chemical probes for HBV core protein functions in the future.

乙型肝炎病毒（HBV）是慢性肝病的病原体，与随后的肝硬化和肝细胞癌的发展相关。目前使用核苷（酸）类似物的抗病毒治疗可有效抑制病毒复制和中断疾病进展，但很少能完全治愈 HBV。因此，对于开发新型抗HBV药物的需求仍未得到满足。在这里，我们报告N的识别-(4-硝基苯基)-1-苯乙酮腙 (ANPH) 作为一种新型结构类选择性抑制剂，使用腺病毒载体介导的 HBV 基因组转导靶向 HBV 基因组的复制。ANPH 通过诱导形成没有前基因组 RNA 的空衣壳而不影响其转录和翻译来抑制 HepG2.2.15 细胞中的病毒基因组复制。使用由组装结构域组成的截短核心蛋白的生化分析表明，ANPH 加速了形态完整衣壳的形成。综上所述，我们提出 ANPH 可能提供一种新的结构支架来设计药物化学中的新抗 HBV 药物以及未来 HBV 核心蛋白功能的化学探针。