Study of potential blocking peptides targeting the SARS-CoV-2 RBD/hACE2 interaction

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, was declared a public health emergency in early 2020. The infection initiates when the receptor-binding domain (RBD) of the viral Spike protein binds to human angiotensin-converting enzyme 2 (ACE2). Despite the success of vaccination efforts, the emergence of new variants highlights the ongoing need for treatments targeting these evolving strains. In silico methods three peptides were previously identified—BP2, BP9, and BP11—capable of disrupting the RBD-ACE2 interaction, though their efficacy has not been experimentally validated until now. In this study, these peptides were recombinantly produced in Komagataella phaffii and purified via affinity chromatography. Their activity was assessed by binding assays with multiple RBD variants and inhibition of the RBD-ACE2 interaction. BP2 showed the highest production yield and exhibited superior affinity and the lowest IC50 among the peptides tested. These results suggest that BP2, in particular, holds promise for developing new therapeutic approaches against SARS-CoV-2 and related coronaviruses.