| Since it is unlikely that HBV can be completely eliminated with current therapies, the development of novel agents with mechanisms that differ from those current therapies is underway worldwide. Specifically, there are two main approaches aiming to eliminate HBV: (1) direct-acting antiviral agents (DAAs), which target the replication cycle and directly inhibit HBV and (2) drugs that act on host factors, mainly inducing HBV-specific immune responses. HBV RNA inhibitors such as small interfering RNAs (siRNA) and anti-sense oligonucleotides (ASO) are in clinical trials. In addition, a novel class of oral HBV antiviral drug belonging to the dihydroquinolizinones (DHQ) class, which acts as an RNA destabilizer by inhibiting the RNA-binding protein PAPD5/7, destabilizing HBV RNA and promoting its degradation. As we recently developed, a SAG compound, a novel RNA destabilizer, is an orally available and well-tolerated drug that potently suppresses HBsAg (minimum effective dose; 6 mg/kg/day) and in combination with NAs markedly reduced both HBsAg and HBV-DNA. Furthermore, the safety examination in mice and monkeys showed that the SAG compound had no apparent toxicity. In this lecture, we introduce novel compounds to achieve functional cure of hepatitis B and discuss future aspects of ant-HBV strategies. |
