Hepatitis B core protein as a therapeutic target

Area of Science:

• Hepatology
• Virology
• Immunology

Background:

• Chronic Hepatitis B virus (HBV) infection is challenging to cure due to persistent viral DNA and immune evasion.
• Current therapies like nucleos(t)ide analogues and pegylated-interferon have limitations in achieving complete viral clearance and seroclearance.
• Novel therapeutic strategies are needed to target alternative steps in the HBV life cycle.

Purpose of the Study:

• To review the hepatitis B core antigen (HBcAg) as a potential therapeutic target for chronic HBV infection.
• To discuss the structure and functions of HBcAg relevant to viral replication and pathogenesis.
• To evaluate the therapeutic potential of targeting HBcAg, particularly core protein allosteric modulators (CpAM).

Main Methods:

• Review of existing literature on HBcAg structure, function, and its role in the HBV life cycle.
• Analysis of in vitro and in vivo studies investigating HBcAg as a therapeutic target.
• Evaluation of clinical trial data for agents targeting HBcAg, with a focus on CpAM.

Main Results:

• HBcAg plays multiple essential roles in HBV replication, including nucleocapsid assembly, RNA encapsidation, and immune modulation.
• Several HBcAg functions have been identified as potential therapeutic targets, with promising results in preclinical studies.
• Core protein allosteric modulators (CpAM) have emerged as a leading class of HBcAg-targeting agents, showing promise in early clinical trials.

Conclusions:

• HBcAg represents a critical and versatile target for developing novel curative therapies for chronic HBV infection.
• CpAM are a promising therapeutic strategy, with further controlled trials needed to confirm their efficacy and safety.
• Exploring drugs targeting other HBcAg functions could offer complementary or alternative approaches to maximize cure rates for HBV.