Interferon-α and inosine pranobex-mediated inhibition of reploication of human RNA viruses in vitro

Interferon- a (IFN-a), produced by immune cells, exhibits pleiotropic anti- viral activity. Inosine pranobex (PI), a synthetic derivative of a purine, shows direct anti- viral activity, and also acts indirectly, by activation of immune cells. The aim of this study was to evaluate an in vitro inhibition of Coxackievirus A16 (CAI6), enterovirus 71 (EV71) and human parainfluenza virus 4 (HPIV-4) replication by PI in combination with IFN-a. In the present study we evaluated an in vitro effect of interferon-a and inosine pranobex on replication ofRNAviruses: CA-16, EV71, HPIV-4. Antiviral effects of IFN-a and IPwere assessed by phenotypic assays. The yield reduction assay (YRA), which evaluates the ability of the compounds to inhibit virus multiplication in cell cultures, was ap- plied. The Reed-Muench statistical method was used to determine the 50% end point (IC51). Our studies have shown that combination of IFN-a and inosine pranobex dis- play higher efficacy than treatment with either compound alone, and suggest syn- ergy that may increase therapeutic effectiveness. The reduction of the average viral ti- ters of EV71, CA-16 and HPIV-4 in A549 cell culture after applying 400 Ig/mL Ip and IFN-a (1000 IU/mL), in comparison to the viral titer in the control was reduced by 1,76 log,, TCID,,/ml, o 3,00 log, TCID50/ml , and 1,60 log,( TCID50/ml respec- tively. The antiviral activity of the tested compounds was also analyzed on the basis of IC., values. Application of 1000 IU/ml IFN-a, with PI after infection of A549 cells with mention above viruses reduced the IC,, by 3,5%, 41,3% and 29% respectively. Our study demonstrated that enhanced antiviral activity was observed when cells infected with RNA viruses were treated with combination of IFN-a and IP. The ef- fectiveness of IFN-a and IP under these conditions has not been previously reported. CA16 virus turned out to be the most sensitive to the action of used inhibitors.