Peptide Platform as a Powerful Tool in the Fight against COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a globalpandemic causing over 195 million infections and more than 4 million fatalities as of July 2021. Todate, it has been demonstrated that a number of mutations in the spike glycoprotein (S protein) ofSARS-CoV-2 variants of concern abrogate or reduce the neutralization potency of several therapeuticantibodies and vaccine-elicited antibodies. Therefore, the development of additional vaccine platformswith improved supply and logistic profile remains a pressing need. In this work, we havevalidated the applicability of a peptide-based strategy focused on a preventive as well as a therapeuticpurpose. On the basis of the involvement of the dipeptidyl peptidase 4 (DPP4), in addition to theangiotensin converting enzyme 2 (ACE2) receptor in the mechanism of virus entry, we analyzedpeptides bearing DPP4 sequences by protein-protein docking and assessed their ability to blockpseudovirus infection in vitro. In parallel, we have selected and synthetized peptide sequenceslocated within the highly conserved receptor-binding domain (RBD) of the S protein, and we foundthat RBD-based vaccines could better promote elicitation of high titers of neutralizing antibodiesspecific against the regions of interest, as confirmed by immunoinformatic methodologies and in vivostudies. These findings unveil a key antigenic site targeted by broadly neutralizing antibodies andpave the way to the design of pan-coronavirus vaccines.