Screening of Peptides as Broad-spectrum Neuraminidase Inhibitors against Influenza Viruses
In this study,a random duodecimal peptides phage display library was probed with influenza A viruses H1N1 and H3N2,resulting in the identification of 52 positive phage clones by using ELISA and neuraminidase inhibition assay.Based on analysis of peptide sequences displayed by positive phage clones,we picked up six peptides to synthesize which are conserved among several clones,respectively.Among these peptides,54-N1 and 69N2 had strong inhibitory activity against influenza A viral neuraminidase N1 and N2 as well as influenza type B neuraminidase,with IC50 7.486-14.693μmol/L for 54-N1 and IC50 6.605-13.007μmol/L for 69-N2.Peptides 54-N1 and 69-N2 inhibited plaque formation of influenza A and B viruses,with IC50 ranging from 18.38 to 31.76μmol/L and 16.56 to 25.49μmol/L,respectively.No cytotoxicity was observed with 54-N1 and 69-N2 at up to 10mmol/L.Also,54-N1 and 69-N2 were compared with Oseltamivir by neuraminidase inhibition assay and plaque formation assay.54-N1 and 69-N2 peptides therefore have potential values in development of nasal spray as new NA inhibitors for broad-spectrum antivirus therapy.