{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:59:51Z","timestamp":1787061591141,"version":"build-2736575974"},"reference-count":57,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T00:00:00Z","timestamp":1695513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR)"},{"name":"Yong Loo Lin School of Medicine (NUS)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Chronic infection with hepatitis B virus (HBV) is incurable, as the current therapeutics cannot eliminate its persistent genomic material, cccDNA. Screening systems for cccDNA-targeting therapeutics are unavailable, as low copies of cccDNA in vitro complicate detection. To address this, cccDNA copies were massively increased to levels detectable via automated plate readers. This was achieved via continuous infection in a contact-free co-culture of an HBV generator (clone F881), which stably produced clinically relevant amounts of HBV, and HBV acceptors selected to carry high cccDNA loads. cccDNA-targeted therapeutics were then identified via reduced cccDNA-specific fluorescence, taking differences in the cell numbers and viability into account. Amongst the drugs tested, the H1 antihistamine Bilastine, HBVCP inhibitors and, surprisingly, current HBV therapeutics downregulated the cccDNA significantly, reflecting the assay\u2019s accuracy and sensitivity in identifying drugs that induce subtle changes in cccDNA levels, which take years to manifest in vivo. Bilastine was the only therapeutic that did not reduce HBV production from F881, indicating it to be a novel direct suppressor of cccDNA levels. When further assessed, only the structurally similar antihistamines Pitolisant and Nizatidine suppressed cccDNA levels when other H1 antihistamines could not. Taken together, our rapid fluorescence cccDNA-targeted drug screen successfully identified a class of molecules with the potential to treat hepatitis B.<\/jats:p>","DOI":"10.3390\/biom13101438","type":"journal-article","created":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T10:36:26Z","timestamp":1695551786000},"page":"1438","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["cccDNA-Targeted Drug Screen Reveals a Class of Antihistamines as Suppressors of HBV Genome Levels"],"prefix":"10.3390","volume":"13","author":[{"given":"Ee Chee","family":"Ren","sequence":"first","affiliation":[{"name":"Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, #03-06, Singapore 138648, Singapore"},{"name":"Immunology Translational Research Programme, Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Block MD4, Level 3, Singapore 117545, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole Ziyi","family":"Zhuo","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, #03-06, Singapore 138648, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi Yi","family":"Goh","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, #03-06, Singapore 138648, Singapore"},{"name":"Immunology Translational Research Programme, Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Block MD4, Level 3, Singapore 117545, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8261-6794","authenticated-orcid":false,"given":"Isabelle","family":"Bonne","sequence":"additional","affiliation":[{"name":"Immunology Translational Research Programme, Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Block MD4, Level 3, Singapore 117545, Singapore"},{"name":"Electron Microscopy Unit, Yong Loo Lin School of Medicine, National University of Singapore, MD1, Tahir Foundation Building, #B1-01, 12 Science Drive 2, Singapore 117549, Singapore"},{"name":"Immunology Programme, Life Sciences Institute, Center for Life Sciences, National University of Singapore, #05-02, 28 Medical Drive, Singapore 117456, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9658-7528","authenticated-orcid":false,"given":"Beno\u00eet","family":"Malleret","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, #03-06, Singapore 138648, Singapore"},{"name":"Immunology Translational Research Programme, Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Block MD4, Level 3, Singapore 117545, Singapore"},{"name":"Electron Microscopy Unit, Yong Loo Lin School of Medicine, National University of Singapore, MD1, Tahir Foundation Building, #B1-01, 12 Science Drive 2, Singapore 117549, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Ling","family":"Ko","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, #03-06, Singapore 138648, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e64","DOI":"10.1038\/emi.2014.64","article-title":"Persistence of hepatitis B virus covalently closed circular DNA in hepatocytes: Molecular mechanisms and clinical significance","volume":"3","author":"Yang","year":"2014","journal-title":"Emerg. 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