Human ACE2 peptide-mimics block SARS-CoV-2 pulmonary cells infection
Philippe Karoyan, Vincent Vieillard, Luis Gómez‐Morales, Estelle Odile, Amélie Guihot, Charles‐Édouard Luyt, Alexis Denis, Pascal Grondin, Olivier Lequin
Abstract
Abstract 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).