Human ACE2 peptide-mimics block SARS-CoV-2 pulmonary cells infection

• Published in: Communications biology Vol. 4; no. 1; p. 197
• Main Authors: Karoyan, Philippe, Vieillard, Vincent, Gómez-Morales, Luis, Odile, Estelle, Guihot, Amélie, Luyt, Charles-Edouard, Denis, Alexis, Grondin, Pascal, Lequin, Olivier
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.02.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 101/58; 13/31; 631/154/309/2420; 692/699/255/2514; 82/75; ACE2; Amino Acid Sequence; Angiotensin; Angiotensin-converting enzyme 2; Angiotensin-Converting Enzyme 2 - chemistry; Binding sites; Biology; Biomedical and Life Sciences; Cell Line; Circular Dichroism; Coronaviruses; COVID-19; COVID-19 - virology; Humans; Immunology; Infections; Life Sciences; Mimicry; Peptides; Peptides - chemical synthesis; Peptides - chemistry; Peptides - metabolism; Peptides - pharmacology; Peptidyl-dipeptidase A; Protein Binding - drug effects; Protein Structure, Secondary; Proteins; SARS-CoV-2 - physiology; Severe acute respiratory syndrome coronavirus 2; Spike glycoprotein; Spike Glycoprotein, Coronavirus - metabolism; Spike protein; Virus Replication - drug effects
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-021-01736-8

In light of the recent accumulated knowledge on SARS-CoV-2 and its mode of human cells invasion, the binding of viral spike glycoprotein to human Angiotensin Converting Enzyme 2 (hACE2) receptor plays a central role in cell entry. We designed a series of peptides mimicking the N -terminal helix of hACE2 protein which contains most of the contacting residues at the binding site, exhibiting a high helical folding propensity in aqueous solution. Our best peptide-mimics are able to block SARS-CoV-2 human pulmonary cell infection with an inhibitory concentration (IC 50 ) in the nanomolar range upon binding to the virus spike protein with high affinity. These first-in-class blocking peptide mimics represent powerful tools that might be used in prophylactic and therapeutic approaches to fight the coronavirus disease 2019 (COVID-19). Karoyan et al. present a method to inhibit SARS-CoV-2 by means of a peptide-mimic approach. They design a series of peptides mimicking the N-terminal helix of hACE2 protein and their best peptide-mimic blocks SARS-CoV-2 human pulmonary cell infection with an IC50 in nanomolar range.