Identification of antiviral mimetic peptides with interferon α-2b-like activity from a random peptide library using a novel functional biopanning method

Abstract

To screen for interferon (IFN) alpha-2b mimetic peptides with antiviral activity. Selecting IFN receptor-binding peptides from a phage-display heptapeptide library using a novel functional biopanning method. This method was developed to identify peptides with activity against vesicular stomatitis virus (VSV) inducing cytopathic effects on WISH cells. Sixteen positive clones were obtained after 3 rounds of functional selection. Ten clones were picked from these positive clones according to the results of phage ELISA and were sequenced. The amino acid sequences homologous to IFN alpha-2b were defined by residues AB loop 31-37, BC loop 68-74, C helix 93-99, CD loop 106-112, D helix 115-121, DE loop 132-138, and E helix 143-161. Two of the peptides, designated clones T3 and T9, aligned with the IFNAR2-binding domains (AB loop and E helix), were synthesized and designated as IR-7 and KP-7, respectively. Both KP-7 and IR-7 were found to compete with GFP/IFN alpha-2b for receptor binding and mimicked the antiviral activity of IFN alpha -2b cooperatively. Two IFN alpha-2b mimetic peptides with antiviral activity were derived from a phage-display heptapeptide library using a novel functional selection method.