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

The continuous and rapid spread of the COVID-19 pandemic has emphasized the need to
seek new therapeutic and prophylactic treatments. Peptide inhibitors are a valid alternative approach
for the treatment of emerging viral infections, mainly due to their low toxicity and high
efficiency. Recently, two small nucleotide signatures were identified in the genome of some members
of the Coronaviridae family and many other human pathogens. In this study, we investigated
whether the corresponding amino acid sequences of such nucleotide sequences could have effects
on 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 coronaviruses
in a dose-dependent manner by binding the RBD of the Spike protein, as suggested by molecular
docking and validated by biochemical studies. The peptides tested do not provide toxicity on cultured
cells or human erythrocytes and are resistant to human serum proteases, indicating that they
may be very promising antiviral peptides.