Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Strategies to Inhibit Hepatitis B Virus Gene Transcription

Version 1 : Received: 5 June 2021 / Approved: 7 June 2021 / Online: 7 June 2021 (12:43:06 CEST)

A peer-reviewed article of this Preprint also exists.

Qu, B.; Brown, R.J.P. Strategies to Inhibit Hepatitis B Virus at the Transcript Level. Viruses 2021, 13, 1327. Qu, B.; Brown, R.J.P. Strategies to Inhibit Hepatitis B Virus at the Transcript Level. Viruses 2021, 13, 1327.

Journal reference: Viruses 2021, 13, 1327
DOI: 10.3390/v13071327

Abstract

Approximately 240 million people are chronically infected with hepatitis B virus (HBV), despite four decades of an effective HBV vaccine. During chronic infection, HBV forms two distinct templates responsible for viral gene 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, and their impact on the stability of 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 and small interfering RNAs and single-stranded oligonucleotides result in transcript degradation from both cccDNA and integrant templates. These antivirals mediate their effects by reducing viral transcripts abundance, eventually leading to loss of surface antigen expression, and 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.

Keywords

chronic hepatitis B; covalently closed circular DNA; viral integration; transcription factor; nuclear receptor; transcriptional inhibitor; RNA interference

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