Helioxanthin analogue 8-1 inhibits duck hepatitis B virus replication in cell culture.
BACKGROUND
Current approved anti-HBV treatment cannot completely eliminate HBV infection, and emergence of resistant virus is an important treatment issue. Effective anti-HBV agents with different mechanisms of action on novel target sites are needed for the treatment of HBV infection and for combating the resistant virus, alone or in combination with current anti-HBV strategies. Helioxanthin analogue 8-1 displayed potent anti-HBV activity in human HBV in vitro and in animal models, with a unique antiviral mechanism. Its antiviral activity in other HBV system needs further study.


METHODS
The anti-duck hepatitis B virus (DHBV) activity of 8-1, an analogue of a natural product, helioxanthin, was studied in the DHBV inducible cell line, dstet5, in comparison to and in combination with the nucleoside analogue, lamivudine (3TC).


RESULTS
Helioxanthin analogue 8-1 exhibited anti-DHBV activity as demonstrated by quantification of viral DNA, RNA, covalently closed circular DNA and protein synthesis. Analogue 8-1 did not affect the stability of cellular macromolecules and did not have a sustained antiviral effect after drug removal. When DHBV replication was induced, virus-harbouring cells were more susceptible to the cytotoxicity of 8-1 than non-induced cells.


CONCLUSIONS
8-1 exhibited effective inhibition on DHBV replication. The combination of 8-1 with 3TC resulted in additional anti-DHBV activity. Viral induced cells displayed higher susceptibility to 8-1 treatment than non-induced cells. HBV X protein might not be an essential factor in the initiation of the biological activity of 8-1, as demonstrated by its absence in DHBV. These findings warrant further development of 8-1 for the treatment of chronic hepatitis B and its associated diseases.
Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA.
Chunxiao
C
Ying
Shenglan
S
Tan
Yung-Chi
YC
Cheng
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D052117:Benzodioxoles / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D004279:DNA, Viral / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004372:Ducks; D018347:Hepadnaviridae Infections / Q000188:drug therapy*; D015611:Hepatitis B Virus, Duck / Q000187:drug effects* / Q000502:physiology; D019259:Lamivudine / Q000494:pharmacology; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D010793:Phthalazines / Q000737:chemistry* / Q000494:pharmacology*; D012367:RNA, Viral / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014758:Viral Core Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D052117:Benzodioxoles; D004279:DNA, Viral; D017705:Lignans; D010793:Phthalazines; D012367:RNA, Viral; D014758:Viral Core Proteins; C505802:helioxanthin; C556224:helioxanthin 8-1; D019259:Lamivudine