Antiviral Properties of Composition Preparations of Double-Stranded RNA and Human Interferon alpha-2b

Objective: This work aimed to obtain and study the antiviral properties of a preparation for intranasal use containing yeast double-stranded RNA (dsRNA) and recombinant human interferon alpha-2b (IFN-α2b) in a delivery vehicle (molecular construct). Material and methods: Molecular constructs carrying IFN-α2b and dsRNA were obtained by our original method. In present study, we used samples of intranasal dosage forms of three formulations: 50 μg dsRNA and 10, 50 or 100 IU IFN-α2b per one dose. The antiviral activity of composition preparations in vitro was determined in L929 and L-68 cell cultures by suppressing the cytopathic effect of the murine encephalomyocarditis virus (EMCV), Columbia strain. Protective properties of preparations in vivo were studied in male white outbred ICR mice infected intranasally with 10 lethal doses of influenza virus A/Aichi/2/68 (H3N2). The protection coefficient was calculated based on the mortality rates and average life expectancy of animals. Results and discussion: All composition preparations could inhibit the destructive action of the test virus and the number of viable cells in L929 and L-68 cultures increased, while the protective effect was enhanced by increasing the dose of IFN-α2b in the drug formulation. The preparation containing 50 μg dsRNA and 100 IU IFN-α2b per dose had the highest antiviral activity. A composition preparation of the same formulation, when administered intranasally to mice three times according to the therapeutic and prophylactic regimen at a dose of (2.5 mg dsRNA and 5000 IU IFN-α2b)/kg, protected 50% of the animals from death, which was not observed after the administration of dsRNA alone. IFN-α2b at a dose equivalent to its content in the composition preparation had a similar, but less pronounced effect. Conclusion: Results of the experimental study conducted in vitro and in vivo, confirmed the fact that the combination of IFN and its inducer enhances the antiviral effect of the composition preparation compared to the effect of its components used separately. The obtained data indicate the potential for creating an intranasal form of preparations using a combination of interferon and dsRNA incorporated in a delivery system.