COVID-19 is caused by a novel coronavirus called severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). Virus cell entry is mediated through a protein-protein interaction (PPI) between the SARS-CoV-2 spike protein and angiotensin-converting enzyme 2 (ACE2). A series of stapled peptide ACE2 peptidomimetics based on the ACE2 interaction motif were designed to bind the coronavirus S-protein RBD and inhibit binding to the human ACE2 receptor. The peptidomimetics were assessed for antiviral activity in an array of assays including a neutralization pseudovirus assay, immunofluorescence (IF) assay and in-vitro fluorescence polarization (FP) assay. However, none of the peptidomimetics showed activity in these assays, suggesting that an enhanced binding interface is required to outcompete ACE2 for S-protein RBD binding and prevent virus internalization.

中文翻译：

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旨在靶向 SARS-CoV-2 刺突蛋白的装订 ACE2 肽模拟物不会阻止病毒内化

COVID-19 是由一种名为严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的新型冠状病毒引起的。病毒细胞进入是通过 SARS-CoV-2 刺突蛋白和血管紧张素转换酶 2 (ACE2) 之间的蛋白质-蛋白质相互作用 (PPI) 介导的。一系列基于 ACE2 相互作用基序的钉合肽 ACE2 拟肽被设计用于结合冠状病毒 S 蛋白 RBD 并抑制与人 ACE2 受体的结合。在一系列测定中评估了拟肽的抗病毒活性，包括中和假病毒测定、免疫荧光（IF）测定和体外荧光偏振（FP）测定。然而，在这些测定中，没有一种肽模拟物显示出活性，这表明需要增强的结合界面才能在 S 蛋白 RBD 结合方面胜过 ACE2 并防止病毒内化。