Influenza is an acute, highly contagious disease caused by influenza viruses. The fast mutation rate of influenza virus makes it difficult for the development of an effective, lasting vaccine. More attentions were paid on the development of anti-influenza drugs. Influenza viruses are enveloped viruses adapt similar mechanism of virus-ceil membrane fusion of HIV. A serial of conformational changes of fusion protein have been triggered during membrane fusion. The most important event is that a trimer-of-hairpins is formed. Some peptides derived from the glycoprotein of enveloped viruses are able to interfere this process (i.e., T20, a peptide inhibitor of HIV entry). !n our previous work, we have identified a peptide (Pl) that could inhibit membrane fusion of influenza virus. A series of experiments on infected cells and mice have proved that. We are applying a patent for this peptide inhibitor. This proposal aims to optimize PI according to the structure of hemagglutinin protein of influenza virus or glycine scanning mutagenesis and obtain highly effective: and efficient peptide inhibitors against influenza virus.