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.