Antiviral activity and mechanism of ESC-1GN from skin secretion of hylarana guentheri against influenza a virus.

Development of new and effective anti-influenza drugs is critical for prophylaxis and treatment of influenza A virus infection. A wide range of amphibian skin secretions have been identified to show antiviral activity. Our previously reported ESC-1GN, a peptide from the skin secretion of Hylarana guentheri, displayed good antimicrobial and anti-inflammatory effects. Here, we found that ESC-1GN possessed significant antiviral effects against influenza A viruses. Moreover, ESC-1GN could inhibit the entry of divergent H5N1 and H1N1 virus strains with the IC50 values from 1.29 to 4.59 μM. Mechanism studies demonstrated that ESC-1GN disrupted membrane fusion activity of influenza A viruses by interaction with HA2 subunit. The results of site-directed mutant assay and molecular docking revealed that E105, N50 and the residues around them on HA2 subunit could form hydrogen bonds with amino acid on ESC-1GN, which were critical for ESC-1GN binding to HA2 and inhibiting the entry of influenza A viruses. Altogether, these not only suggest that ESC-1GN maybe represent a new type of excellent template designing drugs against influenza A viruses, but also it may shed light on the immune mechanism and survival strategy of H. guentheri against viral pathogens.