Targeted Intracellular Degradation of SARS-CoV-2 RBD via Computationally-Optimized Peptide Fusions

Chatterjee, P.; Ponnapati, M.; Jacobson, J. M.

doi:10.1101/2020.06.01.127829

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bioRxiv · 10.1101/2020.06.01.127829

Targeted Intracellular Degradation of SARS-CoV-2 RBD via Computationally-Optimized Peptide Fusions

Chatterjee, P.·Ponnapati, M.·Jacobson, J. M.

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Abstract

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.

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Chatterjee, P., Ponnapati, M., Jacobson, J. M.. 2020-06-01. Targeted Intracellular Degradation of SARS-CoV-2 RBD via Computationally-Optimized Peptide Fusions. https://doi.org/10.1101/2020.06.01.127829

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