{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T08:34:37Z","timestamp":1788510877601,"version":"build-2803163510"},"reference-count":34,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Okinawa Innovation Ecosystem Joint Research Promotion Project","award":["FT2023\u20132024"],"award-info":[{"award-number":["FT2023\u20132024"]}]},{"name":"Kobayashi Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>We recently reported that onnamide A, a marine-derived natural compound isolated from the sponge Theonella sp., inhibits the entry process of SARS-CoV-2 infection. However, its antiviral activity against other viruses remains largely unexplored. Here, we investigated the effects of onnamide A and its structurally related analog, onnamide B, on hepatitis B virus (HBV) infection. Using iNTCP cells, a hepatoblastoma-derived cell line permissive to HBV infection, we found that onnamides A and B exhibited cytotoxicity, with CC50 values of 0.53 \u00b1 0.10 \u03bcM and 2.37 \u00b1 0.25 \u03bcM, respectively. Following HBV infection, the levels of total HBV RNA were significantly reduced by onnamide A (IC50 = 0.06 \u00b1 0.01 \u03bcM) and onnamide B (IC50 = 0.23 \u00b1 0.06 \u03bcM). Notably, both compounds markedly decreased the levels of HBV pregenomic RNA. Furthermore, significant inhibition was particularly evident when onnamide treatment was initiated after HBV infection. Consistent with these observations, onnamides did not affect HBV binding, entry, or covalently closed circular DNA formation, but they significantly suppressed HBV RNA transcription. In particular, the transcriptional activities driven by the core and X promoters were markedly inhibited by onnamide treatment. Taken together, our findings demonstrate that onnamides possess potent anti-HBV activity and highlight their potential as candidate compounds targeting HBV RNA transcription.<\/jats:p>","DOI":"10.3390\/md24010021","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T09:56:23Z","timestamp":1767347783000},"page":"21","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Onnamides A and B Suppress Hepatitis B Virus Transcription by Inhibiting Viral Promoter Activity"],"prefix":"10.3390","volume":"24","author":[{"given":"Yasuhiro","family":"Hayashi","sequence":"first","affiliation":[{"name":"Faculty of Agriculture, University of Miyazaki, 1-1 Gakuen-kibanadai-nishi, Miyazaki City 889-2192, Miyazaki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sei","family":"Arizono","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture, University of Miyazaki, 1-1 Gakuen-kibanadai-nishi, Miyazaki City 889-2192, Miyazaki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanami","family":"Higa","sequence":"additional","affiliation":[{"name":"Faculty of Science, University of the Ryukyus, 1 Senbaru, Nishihara City 903-0213, Okinawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trianda Ayuning","family":"Tyas","sequence":"additional","affiliation":[{"name":"Faculty of Science, University of the Ryukyus, 1 Senbaru, Nishihara City 903-0213, Okinawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Akahori","sequence":"additional","affiliation":[{"name":"Division of Antiviral Therapy, Joint Research Center for Human Retrovirus Infection, Kagoshima University, 1-21-24 Korimoto, Kagoshima City 890-8544, Kagoshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9424-1491","authenticated-orcid":false,"given":"Kenji","family":"Maeda","sequence":"additional","affiliation":[{"name":"Division of Antiviral Therapy, Joint Research Center for Human Retrovirus Infection, Kagoshima University, 1-21-24 Korimoto, Kagoshima City 890-8544, Kagoshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Toyama","sequence":"additional","affiliation":[{"name":"Department of Virology II, National Institute of Infectious Diseases, Japan Institute for Health Security (JIHS), 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9718-0823","authenticated-orcid":false,"given":"Kanami","family":"Mori-Yasumoto","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Yasumoto-Hirose","sequence":"additional","affiliation":[{"name":"Tropical Technology Plus, 12-75 Suzaki, Uruma City 904-2234, Okinawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Miyakawa","sequence":"additional","affiliation":[{"name":"Influenza Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security, 4-7-1 Gakuen, Musashimurayama City 208-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8672-7379","authenticated-orcid":false,"given":"Junichi","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Faculty of Science, University of the Ryukyus, 1 Senbaru, Nishihara City 903-0213, Okinawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5866-0341","authenticated-orcid":false,"given":"Takahiro","family":"Jomori","sequence":"additional","affiliation":[{"name":"Faculty of Science, University of the Ryukyus, 1 Senbaru, Nishihara City 903-0213, Okinawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,1]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025, November 28). 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