Two novel nonnucleosidic compounds inhibit hepatitis B virus replication by inducing genomefree capsid formation
2nd International Conference on Hepatology
May 09-11, 2016 Chicago, USA

Jian-Ping Zuo

CAS-Shanghai Institute of Materia Medica, China

Posters & Accepted Abstracts: J Liver


Hepatitis B infection is a most common chronic viral infection worldwide. It has long been a difficult pathogen because of its unique life cycle and its ability to integrate into host genome. During the hepatitis B virus life cycle, nucleocapsid assembly is essential for HBV replication. Both RNA reverse transcription and DNA replication occur within the HBV nucleocapsid. We have been dedicating to discover non-nucleosidic anti-HBV agents for more than ten years, and found two series of compounds with anti-HBV activity as assembly effectors. Isothiafludine (NZ-4) is a derivative of bis-heterocycle tandem pairs derived from the natural product leucamide A. It inhibit HBV replication both in vitro and in vivo. NZ-4 is a novel HBV inhibitor with a unique mechanism. Its activity depends on the presence of ARD-I of HBc C-terminal domain. Currently, NZ-4 is being evaluated in phase I clinical trials in China. Another reported nonnucleosidic HBV inhibitor is a Pyridazinone derivative, 3711. It decreases HBV DNA level in cell model system. It interferes with capsid formation by regulating hydrophobic interactions at the interdimer interfaces of HBc N-terminal domain. As aseembly effectors, both compounds induce genome-free capsid formation, without changing capsid morphology. They can also inhibit the replication of various NA-resistant HBV mutants and might provide improved choices to eradicate HBV in the future.

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