Phage displayed peptides recognizing porcine aminopeptidase N inhibit transmissible gastroenteritis coronavirus infection in vitro

Porcine aminopeptidase N (pAPN) is a cellular receptor of transmissible gastroenteritis virus (TGEV), a porcine coronavirus. Interaction between the spike (S) protein of TGEV and pAPN initiates cell infection. Small molecules, especially peptides are an expanding area for therapy or diagnostic assays for viral diseases. Here, the peptides capable of binding the pAPN were, for the first time, identified by biopanning using a random 12-mer peptide library to the immobilized protein. Three chemically synthesized peptides recognizing the pAPN showed effective inhibition ability to TGEV infection in vitro. A putative TxxF motif was identified in the S protein of TGEV. Phages bearing the specific peptides interacted with the pAPN in ELISA. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays confirmed the protective effect of the peptides on cell infection by TGEV. Moreover, the excellent immune responses in mice induced by the identified phages provided the possibility to develop novel phage-based vaccines.