scholarly journals Selective inhibition of the duck hepatitis B virus by a new class of tetraazamacrocycles.

1997 ◽  
Vol 41 (11) ◽  
pp. 2579-2581 ◽  
Author(s):  
O Hantz ◽  
C Borel ◽  
C Trabaud ◽  
F Zoulim ◽  
J Dessolin ◽  
...  

The antiviral activity of a new class of N,N,N',N",NA'''-pentakis (omega-aminoalkyl) tetraazamacrocycles was evaluated in primary duck hepatocyte cultures infected with the duck hepatitis B virus (DHBV). Three of the four tested compounds were able to selectively inhibit DHBV replication by acting at an early step of the hepadnavirus infection but were associated with significant toxicity.

2013 ◽  
Vol 57 (11) ◽  
pp. 5291-5298 ◽  
Author(s):  
Faseeha Noordeen ◽  
Andrew Vaillant ◽  
Allison R. Jilbert

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.


1988 ◽  
Vol 62 (3) ◽  
pp. 861-865 ◽  
Author(s):  
F Imazeki ◽  
K Yaginuma ◽  
M Omata ◽  
K Okuda ◽  
M Kobayashi ◽  
...  

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