Nucleic acid polymers prevent the establishment of duck hepatitis B virus infection in vivo.
Nucleic acid polymers (NAPs) are novel, broad-spectrum antiviral compounds that use the sequence-independent properties of phosphorothioate oligonucleotides (PS-ONs) as amphipathic polymers to block amphipathic interactions involved in viral entry. Using the duck hepatitis B virus (DHBV) model of human hepatitis B virus infection, NAPs have been shown to have both entry and postentry antiviral activity against DHBV infection in vitro in primary duck hepatocytes (PDH). In the current study, various NAPs were assessed for their prophylactic activity in vivo against DHBV infection in ducks. The degenerate NAP REP 2006 prevented the development of widespread and persistent DHBV infection in 14-day-old ducks, while the acidic-pH-sensitive NAP REP 2031 had little or no prophylactic effect. REP 2006 displayed significant toxicity in ducks, which was attributed to CpG-mediated proinflammation, while REP 2031 (which has no CpG motifs) displayed no toxicity. A third NAP, REP 2055, which was designed to retain amphipathic activity at acidic pH and contained no CpG motifs, was well tolerated and displayed prophylactic activity against DHBV infection at doses as low as 1 mg/kg of body weight/day. These studies suggest that NAPs can be easily and predictably tailored to retain anti-DHBV activity and to have minimal toxic effects in vivo. Future studies are planned to establish the therapeutic efficacy of NAPs against persistent DHBV infection.
School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia.
Faseeha
F
Noordeen
Andrew
A
Vaillant
Allison R
AR
Jilbert
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D018899:CpG Islands; D004334:Drug Administration Schedule; D018347:Hepadnaviridae Infections / Q000188:drug therapy* / Q000821:virology; D015611:Hepatitis B Virus, Duck / Q000187:drug effects* / Q000254:growth & development; D006524:Hepatitis, Viral, Animal / Q000188:drug therapy* / Q000821:virology; D057927:Hydrophobic and Hydrophilic Interactions; D054735:Phosphorothioate Oligonucleotides / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D053586:Virus Internalization / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D054735:Phosphorothioate Oligonucleotides