{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:48:00Z","timestamp":1791488880953,"version":"4.3.4"},"reference-count":53,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,6,3]],"date-time":"2023-06-03T00:00:00Z","timestamp":1685750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development (AMED)","doi-asserted-by":"publisher","award":["JP22fk0210075"],"award-info":[{"award-number":["JP22fk0210075"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development (AMED)","doi-asserted-by":"publisher","award":["JP23fk0210132"],"award-info":[{"award-number":["JP23fk0210132"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development (AMED)","doi-asserted-by":"publisher","award":["JP21am0101084 (support number 2810)"],"award-info":[{"award-number":["JP21am0101084 (support number 2810)"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Platform Project for Supporting Drug Discovery and Life Science Research","doi-asserted-by":"publisher","award":["JP22fk0210075"],"award-info":[{"award-number":["JP22fk0210075"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Platform Project for Supporting Drug Discovery and Life Science Research","doi-asserted-by":"publisher","award":["JP23fk0210132"],"award-info":[{"award-number":["JP23fk0210132"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Platform Project for Supporting Drug Discovery and Life Science Research","doi-asserted-by":"publisher","award":["JP21am0101084 (support number 2810)"],"award-info":[{"award-number":["JP21am0101084 (support number 2810)"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms24119708","type":"journal-article","created":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T04:01:47Z","timestamp":1685937707000},"page":"9708","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Masitinib Inhibits Hepatitis A Virus Replication"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2681-0776","authenticated-orcid":false,"given":"Reina","family":"Sasaki-Tanaka","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshikatsu","family":"Shibata","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4617-508X","authenticated-orcid":false,"given":"Mitsuhiko","family":"Moriyama","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2355-7309","authenticated-orcid":false,"given":"Hirofumi","family":"Kogure","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asuka","family":"Hirai-Yuki","sequence":"additional","affiliation":[{"name":"Division of Experimental Animal Research, National Institute of Infectious Diseases, Tokyo 208-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0827-0964","authenticated-orcid":false,"given":"Hiroaki","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1654-5385","authenticated-orcid":false,"given":"Tatsuo","family":"Kanda","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6653","DOI":"10.1016\/j.vaccine.2010.08.037","article-title":"Hepatitis A virus seroprevalence by age and world region, 1990 and 2005","volume":"28","author":"Jacobsen","year":"2010","journal-title":"Vaccine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1002\/lt.25658","article-title":"Changing Etiologies and Prognostic Factors in Pediatric Acute Liver Failure","volume":"26","author":"Mendizabal","year":"2020","journal-title":"Liver Transpl."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/S0140-6736(10)60274-7","article-title":"Acute liver failure","volume":"376","author":"Bernal","year":"2010","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1002\/hep.22177","article-title":"Acute liver failure: Summary of a workshop","volume":"47","author":"Lee","year":"2008","journal-title":"Hepatology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1111\/hepr.13345","article-title":"Deteriorated outcome of recent patients with acute liver failure and late-onset hepatic failure caused by infection with hepatitis A virus: A subanalysis of patients seen between 1998 and 2015 and enrolled in nationwide surveys in Japan","volume":"8","author":"Nakao","year":"2019","journal-title":"Hepatol. 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