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 (IC₅₀) 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).

鉴于最近对SARS-CoV-2及其人类细胞侵袭模式的积累知识，病毒刺突糖蛋白与人类血管紧张素转化酶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末端螺旋的肽，该肽在结合位点包含大多数接触残基，在水溶液中表现出很高的螺旋折叠倾向。我们最好的肽模拟物能够以抑制浓度（IC _50）阻断SARS-CoV-2人肺细胞感染当以高亲和力结合到病毒刺突蛋白上时，在纳摩尔范围内）。这些一流的阻断肽模拟物代表了强大的工具，可用于预防和治疗2019年冠状病毒疾病（COVID-19）的方法。