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Targeted intracellular degradation of SARS-CoV-2 via computationally optimized peptide fusions.

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.

SUBMITTER: Chatterjee P

PROVIDER: S-EPMC7683566 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Targeted intracellular degradation of SARS-CoV-2 via computationally optimized peptide fusions.

Chatterjee Pranam P Ponnapati Manvitha M Kramme Christian C Plesa Alexandru M AM Church George M GM Jacobson Joseph M JM

Communications biology 20201123 1

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 degra ...[more]

PMID: 33230174

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