Drugs in Development for Hepatitis B Targeting cccDNA

Resumen

To completely eliminate HBV infection, the total eradication of covalently closed circular DNA (cccDNA), the mini-chromosome that provides the template for transcription of all viral mRNAs, would be required. Nuclear cccDNA accumulates in hepatocyte nuclei where it persists as a stable epigenome. Because the HBV genome is integrated into the host cell with this persistence of cccDNA a complete cure in which all cccDNA and integrated virus is eliminated is not something we currently have but is considered the ultimate aim of future therapies. The dozens of experimental CHB treatments currently being developed fall into two main categories: direct-acting antivirals that impede viral replication at a specific point and host-targeting agents that modify host cell function in a way that inhibits viral replication, including both immune modulators and agents that target other host functions. Each of these can target cccDNA directly or indirectly. Discussed here are agents currently in the clinical stage of development for CHB treatment that target cccDNA directly and those that may affect cccDNA indirectly.