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Masitinib Inhibits Hepatitis A Virus Replication.

Reina Sasaki-Tanaka1, Toshikatsu Shibata1, Mitsuhiko Moriyama1

  • 1Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan.

International Journal of Molecular Sciences
|June 10, 2023
PubMed
Summary

Researchers developed a new cell model for screening hepatitis A virus (HAV) drugs. Masitinib, a tyrosine kinase inhibitor, showed significant anti-HAV activity in vitro, suggesting its potential for treating severe HAV infections.

Keywords:
HAVHAV stable repliconHuhT7 cellsdrug screeningmasitinib

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Area of Science:

  • Virology
  • Hepatology
  • Drug Discovery

Background:

  • Hepatitis A virus (HAV) infection causes acute hepatitis and liver failure.
  • Current treatments lack potent anti-HAV drugs, necessitating new therapeutic strategies.
  • Effective drug screening models are crucial for identifying novel antiviral agents.

Purpose of the Study:

  • To establish a novel cell-based model for hepatitis A virus (HAV) drug screening.
  • To identify existing drugs with in vitro anti-HAV activity.
  • To evaluate the therapeutic potential of identified compounds against HAV infection.

Main Methods:

  • Established HuhT7-HAV/Luc cells stably expressing HAV replicon RNA with luciferase reporter.
  • Utilized a PiggyBac-based gene transfer system for cell line development.
  • Screened 1134 US Food and Drug Administration (FDA)-approved drugs for in vitro anti-HAV activity.

Main Results:

  • The HuhT7-HAV/Luc cell system demonstrated efficacy in mimicking HAV replication for drug screening.
  • Tyrosine kinase inhibitor masitinib significantly reduced replication of HAV genotypes IB and IIIA.
  • Masitinib also inhibited the internal ribosomal entry-site (IRES) activity of HAV HM175.

Conclusions:

  • HuhT7-HAV/Luc cells provide a valuable platform for anti-HAV drug discovery.
  • Masitinib exhibits significant in vitro anti-HAV activity and warrants further investigation for treating severe HAV.
  • This study identifies a promising lead compound for developing new hepatitis A therapies.