Antiviral properties of composition drugs based on double-stranded RNA and human interferon alpha-2b

The aim of this work was to obtain and study antiviral properties of a drug for intranasal use containing yeast double-stranded RNA (dsRNA) and recombinant human interferon alpha-2b (IFN-α2b) incorporated into a delivery system (molecular construct). Material and methods. Molecular constructs carrying IFN-α2b and dsRNA were obtained by our original method. For present study, the samples of intranasal dosage forms of three formulations were chosen: 50 µg of dsRNA and 10, 50 or 100 IU of IFN-α2b per one dose. The in vitro antiviral activity of the composition preparations was determined by inhibition of cytopathic effect (CPE) of murine encephalomyocarditis virus (EMCV), Columbia strain, in mouse L929 and L-68 cell cultures. The in vivo protective properties of the preparations were studied in white outbred ICR male mice intranasally infected with 10 lethal dose, 50 %, of influenza virus strain A/Aichi/2/68 (H3N2). The protection coefficient was calculated by average life expectancy and death of animals. Results and discussion. All the composition preparations used in this study demonstrated the ability to inhibit the destructive effect of the test virus and increase the number of viable cells in L929 and L-68 cultures. The enhancement of the protective effect was observed with increasing IFN-α2b content in the drug formulation. The greatest antiviral activity was shown for the preparation containing 50 µg of dsRNA and 100 IU of IFN-α2b per dose. A composition preparation of the same formulation, administered intranasally three times at a dose of (2.5 mg dsRNA and 5000 IU IFN-α2b)/kg according to the therapeutic and prophylactic regimen, protected 50 % of animals from death, which was not observed in a group administered with dsRNA alone. IFN-α2b used at a dose equivalent to its content in the composition preparation had a similar but less pronounced effect. Conclusions. The results of the in vitro and in vivo experiments have confirmed the fact that combining interferon and its inducer enhances the antiviral effect of the composition drug compared to that of its components used separately. The data obtained testify to the prospects for the development of intranasal forms of antiviral drugs using a combination of interferon and dsRNA incorporated in a delivery system.