Difluoromethylornithine, a Decarboxylase 1 Inhibitor, Suppresses Hepatitis B Virus Replication by Reducing HBc Protein Levels

Mao B,  Wang Z,  Pi S,  Long Q,  Chen K,  Cui J,  Huang A,  Hu Y,

Front Cell Infect Microbiol 2020;10

PMID：32373551   DOI：10.3389/fcimb.2020.00158

Current treatments of hepatitis B virus (HBV) are limited to Interferon-alpha or the
nucleos(t)ide analogs antiviral therapies, and it is crucial to develop and define
new antiviral drugs to cure HBV. In this study, we explored the anti-HBV effect of
difluoromethylornithine (DFMO), an irreversibly inhibitor of decarboxylase 1(ODC1) on
HBV replication. Firstly, we found that polyamines contributed to HBV DNA replication
via increasing levels of the HBV core protein (HBc) and capsids. In contrast, depletion
of polyamines either by silencing the expression of ODC1 or DFMO treatment, resulted
in decreasing viral DNA replication and levels of HBc protein and capsids. Furthermore,
we found that DFMO decreased the stability of the HBc protein without affecting mRNA
transcription and protein translation. Taken together, our findings demonstrate that DFMO
inhibits HBV replication by reducing HBc stability and this may provide a new approach
for HBV therapeutics.