1. Academic Validation
  2. Screening of novel drugs for inhibiting hepatitis E virus replication

Screening of novel drugs for inhibiting hepatitis E virus replication

  • J Virol Methods. 2019 Aug;270:1-11. doi: 10.1016/j.jviromet.2019.04.017.
Takashi Nishiyama 1 Tominari Kobayashi 1 Suljid Jirintai 2 Isao Kii 3 Shigeo Nagashima 1 Putu Prathiwi Primadharsini 1 Tsutomu Nishizawa 1 Hiroaki Okamoto 4
Affiliations

Affiliations

  • 1 Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke-Shi, Tochigi 329-0498, Japan.
  • 2 Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke-Shi, Tochigi 329-0498, Japan; Division of Pathology, Department of Basic Veterinary Medicine, Inner Mongolia Agricultural University College of Medicine, Hohhot, Inner Mongolia, China.
  • 3 Common Facilities Unit, Integrated Research Group, Compass to Healthy Life Research Complex Program, RIKEN Cluster for Science, Technology and Innovation Hub, Kobe, Japan.
  • 4 Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke-Shi, Tochigi 329-0498, Japan. Electronic address: [email protected].
Abstract

Hepatitis E, which is caused by hepatitis E virus (HEV), is generally a self-limiting, acute, and rarely fatal disease. It is sometimes fulminant and lethal, especially during pregnancy. Indeed, it occasionally takes a chronic course in immunocompromised individuals. To cure hepatitis E patients, the broad-spectrum antivirals (ribavirin and pegylated interferon α) are used. However, this treatment is insufficient and unsafe in some patients due to embryoteratogenic effects, leukopenia, and thrombocytopenia. In this study, we constructed an HEV replication reporter system with Gaussia luciferase for comprehensively screening anti-HEV drug candidates, and developed a cell-culture system using cells robustly producing HEV to validate the efficacy of anti-HEV drug candidates. We screened anti-HEV drug candidates from United States Food and Drug Administration-approved drugs using the established HEV replication reporter system, and investigated the selected candidates and type III interferons (interferon λ1-3) using the cell-culture system. In conclusion, we constructed an HEV replicon system for anti-HEV drug screening and a novel cell-culture system to strictly evaluate the replication-inhibitory activities of the obtained anti-HEV candidates. Our findings suggested that interferon λ1-3 might be effective for treating hepatitis E.

Keywords

Cell culture; Drug screening; Gaussia luciferase; Hepatitis E virus; Interferon λ1-3.

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