The emergence of highly pathogenic viruses and a high speed of
infection spread put forward the problem of the development of novel
antivirals and their delivery vehicles. In this study, we investigated the
antiviral effect of the previously identified immunostimulatory 19-bp dsRNA (isRNA) with 3'-nucleotide overhangs, which stimulates
interferon α synthesis when delivered using cationic
liposomes consisting of 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosan tetrahydrochloride and
lipid-helper
dioleoylphosphatidylethanolamine and its PEGylated formulation P1500 in vitro and in vivo. In vitro data showed that isRNA/2X3-DOPE complexes protected L929 cells from encephalomyocarditis virus
infection, while isRNA/P1500 complexes were not active, which correlates with their lower transfection activity in cell culture. Comparison of the
interferon-inducing activity of isRNA in BALB/c, CBA and C57Bl/6 mice showed that PEGylated
liposomes significantly enhance the
interferon-inducing activity of isRNA in vivo. The
antiviral efficacy of the isRNA in vivo was considerably affected by the delivery system. The cationic
liposomes 2X3-DOPE did not enhance the
antiviral properties of isRNA in vivo. Similar
liposomes equipped with a PEGylated lipoconjugate provided a pronounced anti-
influenza effect of the isRNA in vivo. Administration of isRNA to C57Bl/6 led to a decrease in virus titers in the lungs and a significant decrease in the severity of the
infection. Administration of a similar formulation to BALB/c mice caused only a mild
antiviral effect at the initial stages of the
infection. The data show that isRNA in combination with the PEGylated delivery system can be considered an effective means of suppressing
influenza A
infection.