Discovering Peptide Inhibitors of the Spike Protein and Human ACE2 Receptor Interaction via Competitive Elution in Phage Display

Abstract

The interaction between the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the human angiotensin-converting enzyme 2 (hACE2) receptor is an advantageous target for the development of therapies for COVID-19. We used an anti spike receptor binding domain (S RBD) antibody (AM122) to competitively elute phage binding to the S RBD in phage display screening to identify a novel peptide that binds the S protein and hACE2 interaction. We identified a peptide sequence (P1: CPLEYHTC) as a possible hit, and the KD was determined to be 2.667 μM, indicating the potential of this peptide sequence as a therapeutic agent. However, we found no inhibition of the spike protein and hACE2 receptor interaction, suggesting that the peptide may not directly bind to the hACE2 binding site on S RBD. Although further studies are needed, the competitive elution method in phage display screening appears to be an effective method for elucidating onsite peptide sequences that target protein-protein interactions (PPIs).