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.