Antiviral Activity of Various 1-(2′-Deoxy-β-d-lyxofuranosyl), 1-(2′-Fluoro-β-d-xylofuranosyl), 1-(3′-Fluoro-β-d-arabinofuranosyl), and 2′-Fluoro-2′,3′-didehydro-2′,3′-dideoxyribose Pyrimidine Nucleoside Analogues against Duck Hepatitis B Virus (DHBV) and Human Hepatitis B Virus (HBV) Replication

2010 ◽  
Vol 53 (19) ◽  
pp. 7156-7166 ◽  
Author(s):  
Naveen C. Srivastav ◽  
Neeraj Shakya ◽  
Michelle Mak ◽  
Babita Agrawal ◽  
D. Lorne Tyrrell ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Activity ◽  
Nucleoside Analogues ◽  
Pyrimidine Nucleoside ◽  
Duck Hepatitis B Virus ◽  
Hbv Replication ◽  
Duck Hepatitis ◽  
Human Hepatitis ◽  
B Virus

Validation of biocides against duck hepatitis B virus as a surrogate virus for human hepatitis B virus

2006 ◽  
Vol 64 (4) ◽  
pp. 358-365 ◽  
Author(s):  
A. Sauerbrei ◽  
M. Schacke ◽  
B. Glück ◽  
R. Egerer ◽  
P. Wutzler
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Duck Hepatitis B Virus ◽  
Duck Hepatitis ◽  
Human Hepatitis ◽  
B Virus

scholarly journals In Vitro Characterization of the Anti-Hepatitis B Virus Activity and Cross-Resistance Profile of 2′,3′-Dideoxy-3′-Fluoroguanosine

2006 ◽  
Vol 50 (3) ◽  
pp. 955-961 ◽  
Author(s):  
A.-C. Jacquard ◽  
M.-N. Brunelle ◽  
C. Pichoud ◽  
D. Durantel ◽  
S. Carrouée-Durantel ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Activity ◽  
Drug Resistant ◽  
Free System ◽  
Hbv Replication ◽  
Duck Hepatitis ◽  
Huh7 Cells ◽  
B Virus

ABSTRACT The fluorinated guanosine analog 2′,3′-dideoxy-3′-fluoroguanosine (FLG) was shown to inhibit wild-type (wt) hepatitis B virus (HBV) replication in a human hepatoma cell line permanently expressing HBV. Experiments performed in the duck model of HBV infection also showed its in vivo antiviral activity. In this study, we investigated the mechanism of inhibition of FLG on HBV replication and its profile of antiviral activity against different HBV or duck hepatitis B virus (DHBV) drug-resistant mutants. We found that FLG-triphosphate inhibits weakly the priming of the reverse transcription compared to adefovir-diphosphate in a cell-free system assay allowing the expression of an enzymatically active DHBV reverse transcriptase. It inhibits more potently wt DHBV minus-strand DNA synthesis compared to lamivudine-triphosphate and shows a similar activity compared to adefovir-diphosphate. FLG-triphosphate was most likely a competitive inhibitor of dGTP incorporation and a DNA chain terminator. In Huh7 cells transiently transfected with different HBV constructs, FLG inhibited similarly the replication of wt, lamivudine-resistant, adefovir-resistant, and lamivudine-plus-adefovir-resistant HBV mutants. These results were consistent with those obtained in the DHBV polymerase assay using the same drug-resistant polymerase mutants. In conclusion, our data provide new insights in the mechanism of action of FLG-triphosphate on HBV replication and demonstrate its inhibitory activity on drug-resistant mutant reverse transcriptases in vitro. Furthermore, our results provide the rationale for further clinical evaluation of FLG in the treatment of drug-resistant virus infection and in the setting of combination therapy to prevent or delay drug resistance.

scholarly journals Nucleic Acid Polymers Inhibit Duck Hepatitis B Virus InfectionIn Vitro

2013 ◽  
Vol 57 (11) ◽  
pp. 5291-5298 ◽  
Author(s):  
Faseeha Noordeen ◽  
Andrew Vaillant ◽  
Allison R. Jilbert
Keyword(s):  
Hepatitis B Virus ◽  
Nucleic Acid ◽  
Hepatitis B ◽  
Antiviral Activity ◽  
Type I ◽  
Diverse Range ◽  
Duck Hepatitis B Virus ◽  
Duck Hepatitis ◽  
B Virus

ABSTRACTNucleic acid polymers (NAPs) utilize the sequence-independent properties of phosphorothioate oligonucleotides (PS-ONs) to target protein interactions involved in viral replication. NAPs are broadly active against a diverse range of enveloped viruses that use type I entry mechanisms. The antiviral activity of NAPs against hepatitis B virus (HBV) infection was assessedin vitroin duck hepatitis B virus (DHBV)-infected primary duck hepatocytes (PDH). NAPs efficiently entered PDH in the absence of any transfection agent and displayed antiviral activity at concentrations of 0.01 to 10 μM, measured by their ability to prevent the intracellular accumulation of DHBV surface antigen, which was independent of their nucleotide sequence and was specifically dependent on phosphorothioation. Higher levels of antiviral activity were observed with NAPs 40 nucleotides in length or longer. The fully degenerate NAP (REP 2006) was active during DHBV infection or when added 12 h after infection. In contrast, an acidic-pH-sensitive NAP (REP 2031) that was broadly active against other viruses displayed antiviral activity when present during DHBV infection but no activity when added 12 h after infection, suggesting that NAPs exert their postentry effect in an acidic environment unique to DHBV infection. Both REP 2006 and REP 2031 displayed negligible cytotoxicity in PDH at concentrations of up to 10 μM, as assessed using an XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] cytotoxicity assay. The antiviral activity of NAPs against DHBVin vitrowas strictly dependent on their amphipathic character, suggesting that NAPs interact with amphipathic target(s) that are important for DHBV entry and postentry mechanisms required for infection.

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