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.
【저자키워드】 viral infection, Structure-based drug design, 【초록키워드】 COVID-19, coronavirus disease, SARS-CoV-2, knowledge, Infection, peptide, Prophylactic, IC50, binding site, hACE2, glycoprotein, receptor, binding, Therapeutic approach, angiotensin, Invasion, residue, cell entry, high affinity, powerful tool, viral spike, inhibitory concentration, human cell, N-terminal, virus spike protein, hACE2 protein, block, approach, Cell, exhibiting, accumulated, mimicking, inhibit SARS-CoV-2, 【제목키워드】 SARS-CoV-2, ACE2, Human, Infection, Cell,