Inhibitory effects of aprotinin on influenza A and B viruses in vitro
and in vivo
Abstract
Background: Long-term or frequent use of currently approved
anti-influenza agents has resulted in the emergence of drug-resistant
viruses, necessitating the discovery of new drugs. In this study, we
found aprotinin, a serine protease inhibitor, as an anti-influenza
candidate through screening of compound libraries. Aprotinin has been
previously reported to show inhibitory effects on a few subtypes (e.g.,
seasonal H1N1 and H3N2) of influenza A virus (IAV). However, there were
no reports of its inhibitory effects on the other types of influenza
virus. Therefore, in this study, we investigated the inhibitory effects
of aprotinin against a wide range of influenza viruses in vitro and in
vivo. Methods: We tested the antiviral activity of aprotinin in
Madine-Darby canine kidney (MDCK) cells against seasonal human IAVs,
avian influenza viruses with zoonotic potential, oseltamivir-resistant
IAVs, and influenza B virus. We also tested the antiviral activity of
aprotinin against A/PR/8/34 (H1N1) virus in a mouse model. Results: Our
cell-based assay showed that aprotinin had inhibitory effects on
seasonal human IAVs (H1N1 and H3N2 subtypes), avian IAVs (H5N2, H6N5,
and H9N2 subtypes), an oseltamivir-resistant IAV, and a currently
circulating influenza B virus. We have also confirmed its activity in
mice infected with a lethal dose of influenza virus, showing a
significant increase in survival rate. Conclusions: Our findings suggest
that aprotinin has the capacity to inhibit a wide range of influenza
virus subtypes and should be considered for development as a therapeutic
agent against influenza.