Entecavir is a potent deoxyguanosine nucleoside analog with antiviral activity selective for hepadnaviruses (EC50 = 3.7 nM against the hepatitis B virus (HBV) in cultured 2.2.15 liver cells). In vitro, the active intracellular form of entecavir, entecavir triphosphate, demonstrates a higher binding affinity for HBV DNA polymerase than the natural guanosine triphosphate substrate and effectively inhibits HBV DNA replication at 3 stages in the replication pathway: priming, reverse transcription, and DNA-dependent DNA synthesis. The potential therapeutic bene?ts of entecavir have been demonstrated in woodchuck and duck models of HBV. Activity was con?rmed in phase I/II preclinical studies and entecavir received approval from the U.S. Food and Drug Administration for the treatment of adults with chronic hepatitis B.