Fig. 3.

The small compact genome and the requirement of host cellular enzymes for many stages of the HBV life cycle have been an impediment to antiviral drug development. However, a better understanding of the HBV life cycle has identified several molecular targets and compounds that can disrupt new virion formation. These include viral entry inhibitors, encapsidation inhibitors, and agents that prevent viral assembly and coating. Heteroaryldihydropyrimidines (HAPs) bind to the core particles and lead to their degrada- tion. Another group of compounds that inhibit the encapsidation step are phenylpropena- mides. These compounds directly inhibit formation of the nucleocapsid. Antisense RNA and short interfering RNA (siRNA) have been shown to inhibit viral assembly in vitro and in animal models. Glucosidase inhibitors block the glycosylation of surface proteins during the viral assembly step. Recently, pre-S1 derived lipopeptides were shown to be potent inhibitors of HBV entry and may be useful after liver transplantation and perhaps in chronic hepatitis B. (From Ghany M, Liang TJ. Drug targets and molecular mechanisms of drug resis- tance in chronic hepatitis B. Gastroenterology 2007;132:1574–85; with permission.)