Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke 329-0498, Tochigi, Japan.
Laboratory of Membrane Proteins, Research Division for Quantitative Life Sciences, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Viruses. 2023 Sep 23;15(10):1989. doi: 10.3390/v15101989.
The hepatitis E virus (HEV) is increasingly acknowledged as the primary cause of acute hepatitis. While most HEV infections are self-limiting, cases of chronic infection and fulminant hepatitis necessitate the administration of anti-HEV medications. However, there is a lack of specific antiviral drugs designed for HEV, and the currently available drug (ribavirin) has been associated with significant adverse effects. The development of innovative antiviral drugs involves targeting distinct steps within the viral life cycle: the early step (attachment and internalization), middle step (translation and RNA replication), and late step (virus particle formation and virion release). We recently established three HEV reporter systems, each covering one or two of these steps. Using these reporter systems, we identified various potential drug candidates that target different steps of the HEV life cycle. Through rigorous in vitro testing using our robust cell culture system with the genotype 3 HEV strain (JE03-1760F/P10), we confirmed the efficacy of these drugs, when used alone or in combination with existing anti-HEV drugs. This underscores their significance in the quest for an effective anti-HEV treatment. In the present review, we discuss the development of the three reporter systems, their applications in drug screening, and their potential to advance our understanding of the incompletely elucidated HEV life cycle.
戊型肝炎病毒（HEV）越来越被认为是急性肝炎的主要原因。虽然大多数 HEV 感染是自限性的，但慢性感染和暴发性肝炎的病例需要使用抗 HEV 药物。然而，目前缺乏专门针对 HEV 的抗病毒药物，而现有的药物（利巴韦林）存在显著的不良反应。开发创新的抗病毒药物涉及针对病毒生命周期的不同步骤：早期步骤（附着和内化）、中期步骤（翻译和 RNA 复制）和晚期步骤（病毒颗粒形成和病毒粒子释放）。我们最近建立了三种 HEV 报告系统，每个系统涵盖一个或两个这些步骤。使用这些报告系统，我们确定了各种潜在的药物候选物，这些候选物针对 HEV 生命周期的不同步骤。通过使用我们具有基因型 3 HEV 株（JE03-1760F/P10）的稳健细胞培养系统进行严格的体外测试，我们证实了这些药物单独使用或与现有抗 HEV 药物联合使用的疗效。这突显了它们在寻求有效抗 HEV 治疗方面的重要性。在本综述中，我们讨论了三种报告系统的发展、它们在药物筛选中的应用以及它们在推进我们对不完全阐明的 HEV 生命周期的理解方面的潜力。
