3.5 Inhibitory effects of aprotinin treatment in mice infected with a lethal dose of A/PR/8/34 (H1N1) virus
To test whether aprotinin has antiviral activity in vivo , we tested its effects against lethal A/PR/8/34 (H1N1) virus infection in C57BL/6 mice. We initially treated mice with once-daily intravenous injections of aprotinin. However, while it did not have toxic effectsin vivo , it also did not display antiviral effects in influenza-infected mice (data not shown). The initial half-life of aprotinin may be too short for conferring antiviral effects in vivo . As such, we decided to administer aprotinin twice a day.
C57BL/6 mice were intranasally inoculated with 3 LDĀ­50of A/PR/8/34 (H1N1) virus. For 5 days after infection, the mice received twice-daily intravenous injections of aprotinin or twice-daily oral administrations of oseltamivir or PBS as controls. Bodyweight changes and survival were monitored daily for 14 days following infection (Fig. 7). The PBS-treated mice had 0% survival at 8 days post-infection. Meanwhile, the groups of mice treated with either aprotinin or oseltamivir showed 75% or 100% survival. These results strongly support the antiviral effect of aprotinin against influenza virus infection.