{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T02:52:40Z","timestamp":1771383160220,"version":"3.50.1"},"reference-count":35,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T00:00:00Z","timestamp":1628467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014189","name":"Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry","doi-asserted-by":"publisher","award":["121004-1"],"award-info":[{"award-number":["121004-1"]}],"id":[{"id":"10.13039\/501100014189","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002641","name":"Konkuk University","doi-asserted-by":"publisher","award":["2020-A2019-0264"],"award-info":[{"award-number":["2020-A2019-0264"]}],"id":[{"id":"10.13039\/501100002641","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Hepatitis A virus (HAV), the causative pathogen of hepatitis A, induces severe acute liver injuries in humans and is a serious public health concern worldwide. However, appropriate therapeutics have not yet been developed. The enzyme heme oxygenase-1 (HO-1) exerts antiviral activities in cells infected with several viruses including hepatitis B and C viruses. In this study, we demonstrated for the first time the suppression of virus replication by HO-1 in cells infected with HAV. Hemin (HO-1 inducer) induced HO-1 mRNA and protein expression, as expected, and below 50 mM, dose-dependently reduced the viral RNA and proteins in the HAV-infected cells without cytotoxicity. Additionally, HO-1 protein overexpression using a protein expression vector suppressed HAV replication. Although ZnPP-9, an HO-1 inhibitor, did not affect HAV replication, it significantly inhibited hemin-induced antiviral activity in HAV-infected cells. Additionally, FeCl3, CORM-3, biliverdin, and the HO-1 inducers andrographolide and CoPP inhibited HAV replication in the HAV-infected cells; andrographolide and CoPP exhibited a dose-dependent effect. In conclusion, these results suggest that HO-1 effectively suppresses HAV infection in vitro, and its enzymatic products appear to exert antiviral activity. We expect that these results could contribute to the development of a new antiviral drug for HAV.<\/jats:p>","DOI":"10.3390\/pharmaceutics13081229","type":"journal-article","created":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T21:41:46Z","timestamp":1628545306000},"page":"1229","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Heme Oxygenase-1 Exerts Antiviral Activity against Hepatitis A Virus In Vitro"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6585-8559","authenticated-orcid":false,"given":"Dong-Hwi","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hee-Seop","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyeon-Jeong","family":"Go","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Da-Yoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae-Hyeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1074-8162","authenticated-orcid":false,"given":"Joong-Bok","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung-Yong","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4158-6402","authenticated-orcid":false,"given":"Chang-Seon","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang-Won","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In-Soo","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1128\/jvi.61.1.50-59.1987","article-title":"Complete nucleotide sequence of wild-type hepatitis A virus: Comparison with different strains of hepatitis A virus and other picornaviruses","volume":"61","author":"Cohen","year":"1987","journal-title":"J. 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