Screening of novel drugs for inhibiting hepatitis E virus replication.

Authors:
Takashi Nishiyama
Takashi Nishiyama
Tokyo Institute of Technology
Japan
Suljid Jirintai
Suljid Jirintai
Jichi Medical University School of Medicine
Japan
Isao Kii
Isao Kii
Tokyo Institute of Technology
Japan
Shigeo Nagashima
Shigeo Nagashima
Jichi Medical University School of Medicine
Japan
Putu Prathiwi Primadharsini
Putu Prathiwi Primadharsini
Jichi Medical University School of Medicine
Shimotsuke | Japan
Tsutomu Nishizawa
Tsutomu Nishizawa
Jichi Medical School
Japan
Hiroaki Okamoto
Hiroaki Okamoto
Jichi Medical University School of Medicine
Japan

J Virol Methods 2019 Aug 17;270:1-11. Epub 2019 Apr 17.

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:

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.

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Source
https://linkinghub.elsevier.com/retrieve/pii/S01660934183029
Publisher Site
http://dx.doi.org/10.1016/j.jviromet.2019.04.017DOI Listing
August 2019
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