Javanicin inhibits the secretion of hepatitis B virus particles thorough the proteasome-dependent degradation of core protein.

BACKGROUND

Hepatitis B virus (HBV) is the primary cause of liver disease. Nucleot(s)ide analogues such as Entecavir are commonly used to treat HBV infection; however, although these drugs attenuate the virus, they are not a cure. Therefore, it is important to find a novel anti-HBV compounds that enable complete remission of chronic hepatitis B (CHB) infection.

METHODS

We screened 190 natural product libraries using the HepG2.2.15 cell line. Additionally, anti-HBV activities were assessed across genotypes C and D. The mechanism underlying the inhibition of HBV replication by the identified compound was elucidated through cell-based assays.

RESULTS

We identified a hit compound called Javanicin, which is derived from the endophytic fungus JS169. The IC50 of Javanicin is < 500 nM, and the selectivity index (SI = CC50/IC50) is > 10. Javanicin induced proteasome-mediated degradation of the HBV core protein, and reduced the amount of HBV capsid protein. Javanicin and Entecavir acted synergistically, and were more effective than either drug alone. Additionally, structural analysis showed that Javanicin carries several modifiable moieties, which may lead to development of derivatives.

CONCLUSIONS

Javanicin is a novel class of HBV capsid assembly inhibitors, functioning by inducing proteasome-mediated degradation. Furthermore, when paired with Entecavir, Javanicin holds potential as a curative treatment for CHB.