Hepatitis B Virus Epsilon (ε) RNA Element: Dynamic Regulator of Viral Replication and Attractive Therapeutic Target

Abstract

Hepatitis B virus (HBV) chronically infects millions of people worldwide, which underscores the importance of discovering and designing novel anti-HBV therapeutics to complement current treatment strategies. An underexploited but attractive therapeutic target is ε, a cis-acting regulatory stem-loop RNA situated within the HBV pregenomic RNA (pgRNA). The binding of ε to the viral polymerase protein (P) is pivotal, as it triggers the packaging of pgRNA and P, as well as the reverse transcription of the viral genome. Consequently, small molecules capable of disrupting this interaction hold the potential to inhibit the early stages of HBV replication. The rational design of such ligands necessitates high-resolution structural information for the ε–P complex or its individual components. While these data are currently unavailable for P, our recent structural elucidation of ε through solution nuclear magnetic resonance spectroscopy marks a significant advancement in this area. In this review, we provide a brief overview of HBV replication and some of the therapeutic strategies to combat chronic HBV infection. These descriptions are intended to contextualize our recent experimental efforts to characterize ε and identify ε-targeting ligands, with the ultimate goal of developing novel anti-HBV therapeutics.

Molecular questioning of potential efficacy of epsilon targeted antiviral treatment option for Domestic Cat Hepadnavirus

“…It possesses a unique enzyme that can convert RNA to DNA, which has led some researchers to refer to it as a 'DNA retrovirus' [18,19]. Hepatitis B virus, a homolog of DCH, replicates using closed circular DNA (cccDNA) as an RNA intermediate, also known as pre-genomic RNA (pgRNA) [20]. pgRNA is the critical intermediate form in the replication.…”

“…It is employed like an mRNA for the formation of viral proteins. In the formation of pgRNA, cis-acting RNA or so-called epsilon (ε) binds to its counterpart region on the P protein, and the P-ε packaging complex occurs [20]. This mechanism is probably also present in the replication of DCH.…”