HBV capsid assembly modulators differentially modulate the assembly of wild-type and drug-resistant core protein chimeric nucleocapsids and empty capsids.

ABSTRACT: Multiple capsid assembly modulators (CAMs) are in clinical development for the treatment of chronic hepatitis B. The emergence of CAM-resistant HBV has resulted in the failure of CAM antiviral therapy in recent clinical trials. Because wild-type (WT) and CAM-resistant core protein (Cp) can co-assemble to form chimeric capsids, it is important to understand how CAMs modulate the assembly and disassembly of chimeric capsids and how CAM-resistant HBV variants emerge under CAM antiviral therapy. In addressing these questions, we found that in human hepatoma cells co-transfected with a serial molar ratio of WT and mutant HBV replicons expressing CAM-resistant Cp, expression of as few as 10% WT Cp conferred inhibition of nucleocapsid assembly by CAMs. However, 50% Cp with T33N substitution confe

SUBMITTER: Liu H 

PROVIDER: S-EPMC12342251 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature