Strategies to Inhibit Hepatitis B Virus at the Transcript Level

Abstract

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.

Tannic Acid Suppresses HBV Replication via the Regulation of NF-κB, MAPKs, and Autophagy in HepG2.2.15 Cells

“…For instance, it has been proven that IL-6 and TNF-α could suppress HBV pgRNA transcription by regulating the expression of HNF4α. 28 Similarly, we noted that TA treatment reduced the mRNA expression of HNF4α in HepG2.2.15 (Figure 2G), which was in line with a previous report. 35 In brief, the role of anti-HBV by TA might be contributed to increased inflammatory responses and subsequent transcriptional modulation of antiviral factors.…”

“…In the past years, viral hepatitis has become the seventh leading cause of death worldwide. 28 Despite the application of global vaccination, chronic HBV infection remains a headache for National Health System. 29 Recently, researchers attempted to discover new natural components with anti-HBV effects to compensate for existing therapy's limitations.…”

“…IFN-α fails to inhibit HBV replication directly but triggers the production of antiviral effectors (OAS and MxA). 28 It is notable that the nuclear receptor HNF4α is related to hepatic inflammation-mediated HBV transcription. For instance, it has been proven that IL-6 and TNF-α could suppress HBV pgRNA transcription by regulating the expression of HNF4α.…”

“…In the past years, viral hepatitis has become the seventh leading cause of death worldwide . Despite the application of global vaccination, chronic HBV infection remains a headache for National Health System .…”

Potential of CRISPR/Cas system as emerging tools in the detection of viral hepatitis infection

“…However, the most frequent causative agents of this condition are the hepatotropic viruses, including Hepatitis A virus (HAV), Hepatitis B virus (HBV), Hepatitis C virus (HCV), Hepatitis delta virus (HDV), and Hepatitis E virus (HEV), which lead to either an acute or a chronic infection [ 2 ]. These liver viruses include a variety of DNA and RNA viruses from different viral families that are spread through different transmission routes [ 3 ]. Globally, viral hepatitis causes about 1.4 million deaths each year.…”