Enhanced inhibition of foot-and-mouth disease virus by combinations of porcine interferon-α and antiviral agents

Foot-and-mouth disease (FMD) is an economically significant animal disease because of the speed of its transmission. The current FMD vaccine provides no protection until 7 days after the vaccination, which reduces its effectiveness in the case of an outbreak. Therefore, to find an alternative method of applying antiviral agents for rapid and enhanced inhibition of the FMD virus (FMDV), we compared the antiviral effects of promising antiviral agents and attempted to apply them in combination. First, we measured and compared the 50% effective concentration (EC50) to the mean inhibition effects of FMDV, and the 50% cytotoxic concentration (CC50) to the mean cytotoxicity of antiviral agents such as ribavirin, guanidine-hydrochloride (guanidine-HCl), 6-azauridine, and recombinant adenovirus expressing three small interference RNAs (Ad-siRNA) or porcine interferon-α (Ad-porcine IFN-α) in swine kidney cells (IBRS-2). The selectivity indices of ribavirin (35.2) and 6-azauridine (34.6) were higher than that of guanidine-HCl (26.9). The selectivity indices of Ad-siRNA or Ad-porcine IFN-α were 7 × 103 or 7 × 104 based on the adenoviral titer. Next, we tested the combined effects of the FMDV inhibition agents. Enhanced inhibition effects were observed in the IBRS-2 cells and in suckling mice from the combination of Ad-porcine IFN-α and Ad-siRNA or ribavirin. The combined application of these recombinant adenoviruses and ribavirin may enhance their inhibitory effect on FMDV and overcome FMDV resistance against antiviral agents.

► We measured EC50 and CC50 of the five well-known or potential antiviral agents. ► The antiviral effect against of 6-Azauridine was demonstrated. ► We tested the combination effects of the pairs of antiviral agents. ► Enhanced antiviral effect of Ad-porcine IFN-α with Ribavirin was demonstrated. ► Enhanced antiviral effect of Ad-porcine IFN-α and Ad-siRNA was demonstrated.