Sorbonne Université, École Normale Supérieure, PSL University, CNRS, Laboratoire des Biomolécules, LBM, 75005, Paris, France.
Sorbonne Université, École Normale Supérieure, PSL University, CNRS, Laboratoire des Biomolécules, LBM, Site OncoDesign, 25-27 Avenue du Québec, 91140, Villebon Sur Yvette, France.
Commun Biol. 2021 Feb 12;4(1):197. 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) 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).
鉴于最近关于 SARS-CoV-2 及其入侵人体细胞模式的知识积累，病毒刺突糖蛋白与人体血管紧张素转换酶 2（hACE2）受体的结合在细胞进入中起着核心作用。我们设计了一系列模拟 hACE2 蛋白 N 端螺旋的肽段，该螺旋包含结合位点上的大多数接触残基，在水溶液中具有很高的螺旋折叠倾向。我们最好的肽模拟物能够阻断 SARS-CoV-2 对人类肺细胞的感染，在与病毒刺突蛋白结合时具有高亲和力，其抑制浓度（IC）在纳摩尔范围内。这些首创的阻断肽模拟物代表了强大的工具，可用于预防和治疗 2019 年冠状病毒病（COVID-19）。
