Abstract
Despite a preventive vaccine being available, more than 250 million people suffer from chronic hepatitis B virus (HBV) infection, a major cause of liver disease and HCC. HBV infects human hepatocytes where it establishes its genome, the cccDNA with chromosomal features. Therapies controlling HBV replication exist; however, they are not sufficient to eradicate HBV cccDNA, the main cause for HBV persistence in patients. Core protein is the building block of HBV nucleocapsid. This viral protein modulates almost every step of the HBV life cycle; hence, it represents an attractive target for the development of new antiviral therapies. Capsid assembly modulators (CAM) bind to core dimers and perturb the proper nucleocapsid assembly. The potent antiviral activity of CAM has been demonstrated in cell-based and in vivo models. Moreover, several CAMs have entered clinical development. The aim of this review is to summarize the mechanism of action (MoA) and the advancements in the clinical development of CAMs and in the characterization of their mod of action.
Highlights
A preventive vaccine exists against hepatitis B virus (HBV), around 250 million of people around the world suffer chronic HBV infection, the principal cause of advanced liver disease and hepatocellular carcinoma (HCC) [1,2]
We summarize the molecular and cellular functions of hepatitis B core antigen (HBcAg) in the key steps of the HBV life cycle and highlight the Capsid assembly modulators (CAM) molecules currently in preclinical/clinical development for novel therapeutic strategies
Due to the central role of HBcAg in the HBV life cycle, particular attention has been paid to the discovery and improvement of capsid assembly modulators (CAMs)
Summary
A preventive vaccine exists against hepatitis B virus (HBV), around 250 million of people around the world suffer chronic HBV infection, the principal cause of advanced liver disease and hepatocellular carcinoma (HCC) [1,2]. RNA or the core regions of pregenomic (pg)RNA, the C ORF encodes the hepatitis B e antigen (HBeAg) and the viral nucleocapsid hepatitis B core antigen (HBcAg), respectively. Novel therapeutic strategies for curative approaches (inactivation or the loss of HBV cccDNA) are urgently needed. In this context, HBcAg represents a target of choice for the development of new antivirals as it plays a pivotal role in the HBV life cycle. The core protein allosteric modulators (CAM) are currently under clinical development Their mechanism of action (MoA) remains poorly characterized. We summarize the molecular and cellular functions of HBcAg in the key steps of the HBV life cycle and highlight the CAM molecules currently in preclinical/clinical development for novel therapeutic strategies
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