The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has elicited a global health crisis of catastrophic proportions. With only a few vaccines approved for early or limited use, there is a critical need for effective antiviral strategies. In this study, we report a unique antiviral platform, through computational design of ACE2-derived peptides which both target the viral spike protein receptor binding domain (RBD) and recruit E3 ubiquitin ligases for subsequent intracellular degradation of SARS-CoV-2 in the proteasome. Our engineered peptide fusions demonstrate robust RBD degradation capabilities in human cells and are capable of inhibiting infection-competent viral production, thus prompting their further experimental characterization and therapeutic development.

由新型冠状病毒SARS-CoV-2引起的COVID-19大流行引发了灾难性的全球性健康危机。由于只有少数几种疫苗被批准用于早期或有限使用，因此迫切需要有效的抗病毒策略。在这项研究中，我们报告了一个独特的抗病毒平台，通过ACE2衍生肽的计算设计，该肽既靶向病毒刺突蛋白受体结合域（RBD），又募集E3泛素连接酶用于蛋白酶体中随后的SARS-CoV-2细胞内降解。我们设计的肽融合体在人细胞中显示出强大的RBD降解能力，并能够抑制具有感染能力的病毒产生，从而促进了其进一步的实验表征和治疗开发。