In conclusion, this study demonstrates that h-SH3 can inhibit the replication of influenza A viruses (H1N1, H3N2, and H9N2) at different degrees, and targeting NS1-p85β interaction (PI3K/Akt pathway) or other virus-host interaction may be an attractive strategy against the infection of various influenza A virus subtypes/strains. This evidence concerns the gene AKT1 and infection.