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Masitinib Inhibits Hepatitis A Virus Replication
The hepatitis A virus (HAV) infection causes acute hepatitis. HAV also induces acute liver failure or acute-on-chronic liver failure; however, no potent anti-HAV drugs are currently available in clinical situations. For anti-HAV drug screening, more convenient and useful models that mimic HAV replic...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10253910/ https://www.ncbi.nlm.nih.gov/pubmed/37298659 http://dx.doi.org/10.3390/ijms24119708 |
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author | Sasaki-Tanaka, Reina Shibata, Toshikatsu Moriyama, Mitsuhiko Kogure, Hirofumi Hirai-Yuki, Asuka Okamoto, Hiroaki Kanda, Tatsuo |
author_facet | Sasaki-Tanaka, Reina Shibata, Toshikatsu Moriyama, Mitsuhiko Kogure, Hirofumi Hirai-Yuki, Asuka Okamoto, Hiroaki Kanda, Tatsuo |
author_sort | Sasaki-Tanaka, Reina |
collection | PubMed |
description | The hepatitis A virus (HAV) infection causes acute hepatitis. HAV also induces acute liver failure or acute-on-chronic liver failure; however, no potent anti-HAV drugs are currently available in clinical situations. For anti-HAV drug screening, more convenient and useful models that mimic HAV replication are needed. In the present study, we established HuhT7-HAV/Luc cells, which are HuhT7 cells stably expressing the HAV HM175-18f genotype IB subgenomic replicon RNA harboring the firefly luciferase gene. This system was made by using a PiggyBac-based gene transfer system that introduces nonviral transposon DNA into mammalian cells. Then, we investigated whether 1134 US Food and Drug Administration (FDA)-approved drugs exhibited in vitro anti-HAV activity. We further demonstrated that treatment with tyrosine kinase inhibitor masitinib significantly reduced both HAV HM175-18f genotype IB replication and HAV HA11-1299 genotype IIIA replication. Masitinib also significantly inhibited HAV HM175 internal ribosomal entry-site (IRES) activity. In conclusion, HuhT7-HAV/Luc cells are adequate for anti-HAV drug screening, and masitinib may be useful for the treatment of severe HAV infection. |
format | Online Article Text |
id | pubmed-10253910 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102539102023-06-10 Masitinib Inhibits Hepatitis A Virus Replication Sasaki-Tanaka, Reina Shibata, Toshikatsu Moriyama, Mitsuhiko Kogure, Hirofumi Hirai-Yuki, Asuka Okamoto, Hiroaki Kanda, Tatsuo Int J Mol Sci Article The hepatitis A virus (HAV) infection causes acute hepatitis. HAV also induces acute liver failure or acute-on-chronic liver failure; however, no potent anti-HAV drugs are currently available in clinical situations. For anti-HAV drug screening, more convenient and useful models that mimic HAV replication are needed. In the present study, we established HuhT7-HAV/Luc cells, which are HuhT7 cells stably expressing the HAV HM175-18f genotype IB subgenomic replicon RNA harboring the firefly luciferase gene. This system was made by using a PiggyBac-based gene transfer system that introduces nonviral transposon DNA into mammalian cells. Then, we investigated whether 1134 US Food and Drug Administration (FDA)-approved drugs exhibited in vitro anti-HAV activity. We further demonstrated that treatment with tyrosine kinase inhibitor masitinib significantly reduced both HAV HM175-18f genotype IB replication and HAV HA11-1299 genotype IIIA replication. Masitinib also significantly inhibited HAV HM175 internal ribosomal entry-site (IRES) activity. In conclusion, HuhT7-HAV/Luc cells are adequate for anti-HAV drug screening, and masitinib may be useful for the treatment of severe HAV infection. MDPI 2023-06-03 /pmc/articles/PMC10253910/ /pubmed/37298659 http://dx.doi.org/10.3390/ijms24119708 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sasaki-Tanaka, Reina Shibata, Toshikatsu Moriyama, Mitsuhiko Kogure, Hirofumi Hirai-Yuki, Asuka Okamoto, Hiroaki Kanda, Tatsuo Masitinib Inhibits Hepatitis A Virus Replication |
title | Masitinib Inhibits Hepatitis A Virus Replication |
title_full | Masitinib Inhibits Hepatitis A Virus Replication |
title_fullStr | Masitinib Inhibits Hepatitis A Virus Replication |
title_full_unstemmed | Masitinib Inhibits Hepatitis A Virus Replication |
title_short | Masitinib Inhibits Hepatitis A Virus Replication |
title_sort | masitinib inhibits hepatitis a virus replication |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10253910/ https://www.ncbi.nlm.nih.gov/pubmed/37298659 http://dx.doi.org/10.3390/ijms24119708 |
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