Design of Three Residues Peptides against SARS-CoV-2 Infection

The continuous and rapid spread of the COVID-19 pandemic has emphasized the need toseek new therapeutic and prophylactic treatments. Peptide inhibitors are a valid alternative approachfor the treatment of emerging viral infections, mainly due to their low toxicity and highefficiency. Recently, two small nucleotide signatures were identified in the genome of some membersof the Coronaviridae family and many other human pathogens. In this study, we investigatedwhether the corresponding amino acid sequences of such nucleotide sequences could have effectson the viral infection of two representative human coronaviruses: HCoV-OC43 and SARS-CoV-2.Our results showed that the synthetic peptides analyzed inhibit the infection of both coronavirusesin a dose-dependent manner by binding the RBD of the Spike protein, as suggested by moleculardocking and validated by biochemical studies. The peptides tested do not provide toxicity on culturedcells or human erythrocytes and are resistant to human serum proteases, indicating that theymay be very promising antiviral peptides.