Recent advances in the development of HBV capsid assembly modulators

Hepatitis B virus (HBV) infections represent a significant burden on global public health. Current HBV treatments using nucleos(t)ide analogs (NAs) and PEG interferons cannot fully alleviate this burden as they do not affect the transcriptional activity of the tenacious covalently closed circular DNA (cccDNA) responsible for viral persistence. Capsid assembly modulators (CAMs) disrupt the encapsidation of pre-genomic RNA and can cause nucleocapsid disassembly, thereby affecting multiple steps of HBV replication and reduction of cccDNA pools. This review provides a concise overview of the development of CAMs and the progress achieved in understanding their interactions with HBV core proteins.