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Targeted Intracellular Degradation of SARS-CoV-2 RBD via Computationally-Optimized Peptide Fusions
bioRxiv - Bioengineering Pub Date : 2020-06-01 , DOI: 10.1101/2020.06.01.127829
Pranam Chatterjee , Manvitha Ponnapati , Joseph M. Jacobson

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has elicited a global health crisis of catastrophic proportions. With no approved cure or vaccine currently available, there is a critical need for effective antiviral strategies. In this study, we report a novel 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, thus prompting their further experimental characterization and therapeutic development.

中文翻译:

通过计算优化的多肽融合靶向靶向降解SARS-CoV-2 RBD的细胞内。

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。由于目前没有获得批准的治愈方法或疫苗,因此迫切需要有效的抗病毒策略。在这项研究中,我们报告了一种新型的抗病毒平台,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泛素连接酶用于随后的蛋白酶体中SARS-CoV-2的细胞内降解。 。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,从而促进了它们的进一步实验表征和治疗发展。
更新日期:2020-06-01
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