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Commun Biol
. 2020 Nov 23;3(1):715.
doi: 10.1038/s42003-020-01470-7.
Targeted intracellular degradation of SARS-CoV-2 via computationally optimized peptide fusions
Pranam Chatterjee 1 2 3 4 , Manvitha Ponnapati 5 6 , Christian Kramme 7 8 , Alexandru M Plesa 7 8 , George M Church 7 8 , Joseph M Jacobson 5 6
Affiliations
- PMID: 33230174
- DOI: 10.1038/s42003-020-01470-7
Abstract
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.