Targeting hepatitis B virus cccDNA levels: Recent progress in seeking small molecule drug candidates

Area of Science:

• Hepatology and Virology
• Drug Discovery and Development

Background:

• Hepatitis B virus (HBV) infection is a significant global health concern, leading to cirrhosis and liver cancer.
• The persistence of HBV covalently closed circular DNA (cccDNA) in infected cells prevents a complete cure with current therapies.
• There is a critical need for novel therapeutic strategies to eliminate HBV cccDNA.

Purpose of the Study:

• To review the discovery and optimization of small molecules targeting HBV cccDNA.
• To highlight compounds that inhibit cccDNA synthesis or promote its degradation.

Main Methods:

• Literature review of small molecules designed to reduce HBV cccDNA levels.
• Categorization of compounds based on their mechanism of action against cccDNA.

Main Results:

• Several classes of small molecules have been identified, including cccDNA synthesis inhibitors and reducers.
• Other promising compounds include core protein allosteric modulators, ribonuclease H inhibitors, and HBx inhibitors.
• These molecules offer diverse strategies to lower cccDNA levels in infected cells.

Conclusions:

• Small molecules targeting HBV cccDNA synthesis and degradation represent a promising therapeutic avenue.
• Further development of these compounds could lead to effective treatments for chronic Hepatitis B.
• Reducing cccDNA is crucial for achieving a functional cure for HBV infection.