The MIT Center for Bits and Atoms, Cambridge, MA, 02139, USA.
MIT Media Lab, Massachusetts Institute of Technology (MIT), Cambridge, MA, 02139-4307, USA.
Commun Biol. 2020 Nov 23;3(1):715. doi: 10.1038/s42003-020-01470-7.
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 大流行引发了一场灾难性的全球卫生危机。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，我们报告了一种独特的抗病毒平台，通过计算设计 ACE2 衍生肽，这些肽既能靶向病毒刺突蛋白受体结合域（RBD），又能招募 E3 泛素连接酶，随后在蛋白酶体中对 SARS-CoV-2 进行细胞内降解。我们设计的肽融合物在人细胞中表现出强大的 RBD 降解能力，并且能够抑制有感染能力的病毒产生，因此促使对它们进行进一步的实验表征和治疗开发。
