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Abstract：
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.
摘要：
COVID-19是由一种称为严重急性呼吸道综合症的新型冠状病毒-冠状病毒2（SARS-CoV-2）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。设计了一系列基于ACE2相互作用基序的束缚肽ACE2肽模拟物，以结合冠状病毒S蛋白RBD并抑制与人ACE2受体的结合。在一系列测定中评估肽模拟物的抗病毒活性，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,在这些分析中，没有一个肽模拟物显示出活性，这表明需要增强的结合界面来竞争ACE2与S蛋白RBD结合并防止病毒内化。
