The Basis for Antiviral Therapy: Drug Targets, Cross-Resistance, and Novel Small Molecule Inhibitors

Chronic hepatitis B affects over 300 million people globally, and although there is an effective preventative vaccine, there is no cure. The recent discovery of the NTCP entry receptor means that infection models now permit investigation of drugs that target all stages of HBV life cycle. This is important as existing treatment strategies reduce the viral burden but rarely prevent expression of viral antigens associated with disease progression. It is likely this will only be achieved through the destruction or silencing of cccDNA in the hepatocyte nucleus. In this chapter we describe limitations and advantages of current and emerging treatment and cure strategies for chronic hepatitis B. We also discuss future drug targets with the hepatitis B life cycle that we believe are worthy of investigation. Together, these approaches should speed development of new therapeutic regimens that may lead to HBV cure in the foreseeable future.