Novel Dimeric Capsid Assembly Modulators as a Unique Class of Highly Potent Anti-HBV Agents

Approximately 250 million people are chronic HBV carriers
and are
at high risk of developing hepatitis, cirrhosis, and hepatocellular
carcinoma. Several drugs are currently approved, but because they
do not cure, lifelong therapies are the norm. HBV capsid assembly
modulators (CAMs) have emerged as a promising option, as they lower
several key markers of HBV replication. Novel dimeric structures (D-CAMs)
were designed and evaluated. Their potency and mechanism of action
were compared to those of monomeric D-CAMs, such as GLP-26. Among
them, D-CAM-14 exhibited improved potency over GLP-26 and a unique
effect on capsid morphology and kinetic assembly.