{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T20:51:25Z","timestamp":1776372685910,"version":"3.51.2"},"reference-count":202,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T00:00:00Z","timestamp":1625788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bundesministerium fur Bildung und Forschung (BMBF)","award":["COVID 6b VARIPath"],"award-info":[{"award-number":["COVID 6b VARIPath"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Approximately 240 million people are chronically infected with hepatitis B virus (HBV), despite four decades of effective HBV vaccination. During chronic infection, HBV forms two distinct templates responsible for viral transcription: (1) episomal covalently closed circular (ccc)DNA and (2) host genome-integrated viral templates. Multiple ubiquitous and liver-specific transcription factors are recruited onto these templates and modulate viral gene transcription. This review details the latest developments in antivirals that inhibit HBV gene transcription or destabilize viral transcripts. Notably, nuclear receptor agonists exhibit potent inhibition of viral gene transcription from cccDNA. Small molecule inhibitors repress HBV X protein-mediated transcription from cccDNA, while small interfering RNAs and single-stranded oligonucleotides result in transcript degradation from both cccDNA and integrated templates. These antivirals mediate their effects by reducing viral transcripts abundance, some leading to a loss of surface antigen expression, and they can potentially be added to the arsenal of drugs with demonstrable anti-HBV activity. Thus, these candidates deserve special attention for future repurposing or further development as anti-HBV therapeutics.<\/jats:p>","DOI":"10.3390\/v13071327","type":"journal-article","created":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T10:50:38Z","timestamp":1625827838000},"page":"1327","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Strategies to Inhibit Hepatitis B Virus at the Transcript Level"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7330-2929","authenticated-orcid":false,"given":"Bingqian","family":"Qu","sequence":"first","affiliation":[{"name":"Division of Veterinary Medicine, Paul Ehrlich Institute, 63225 Langen, Germany"},{"name":"European Virus Bioinformatics Center, 07743 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3292-6671","authenticated-orcid":false,"given":"Richard J. P.","family":"Brown","sequence":"additional","affiliation":[{"name":"Division of Veterinary Medicine, Paul Ehrlich Institute, 63225 Langen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/S0140-6736(16)30579-7","article-title":"The global burden of viral hepatitis from 1990 to 2013: Findings from the Global Burden of Disease Study 2013","volume":"388","author":"Stanaway","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.idc.2019.08.004","article-title":"Viral Hepatitis: Etiology, Epidemiology, Transmission, Diagnostics, Treatment, and Prevention","volume":"33","author":"Lanini","year":"2019","journal-title":"Infect. Dis Clin. N. 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