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Review

Strategies to Inhibit Hepatitis B Virus at the Transcript Level

by 1,2,* and 1,*
1
Division of Veterinary Medicine, Paul Ehrlich Institute, 63225 Langen, Germany
2
European Virus Bioinformatics Center, 07743 Jena, Germany
*
Authors to whom correspondence should be addressed.
Academic Editor: Carla S. Coffin
Viruses 2021, 13(7), 1327; https://doi.org/10.3390/v13071327
Received: 5 June 2021 / Revised: 2 July 2021 / Accepted: 6 July 2021 / Published: 9 July 2021
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. View Full-Text
Keywords: chronic hepatitis B; covalently closed circular DNA; viral integration; transcription factor; nuclear receptor; transcriptional inhibitor; RNA interference chronic hepatitis B; covalently closed circular DNA; viral integration; transcription factor; nuclear receptor; transcriptional inhibitor; RNA interference
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MDPI and ACS Style

Qu, B.; Brown, R.J.P. Strategies to Inhibit Hepatitis B Virus at the Transcript Level. Viruses 2021, 13, 1327. https://doi.org/10.3390/v13071327

AMA Style

Qu B, Brown RJP. Strategies to Inhibit Hepatitis B Virus at the Transcript Level. Viruses. 2021; 13(7):1327. https://doi.org/10.3390/v13071327

Chicago/Turabian Style

Qu, Bingqian, and Richard J.P. Brown 2021. "Strategies to Inhibit Hepatitis B Virus at the Transcript Level" Viruses 13, no. 7: 1327. https://doi.org/10.3390/v13071327

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