tetano
Editor, Senior Moderator
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[SUP] 1 2 3 4 [/SUP], Manvitha Ponnapati[SUP] 5 6 [/SUP], Christian Kramme[SUP] 7 8 [/SUP], Alexandru M Plesa[SUP] 7 8 [/SUP], George M Church[SUP] 7 8 [/SUP], Joseph M Jacobson[SUP] 5 6 [/SUP]
Affiliations
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.
. 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[SUP] 1 2 3 4 [/SUP], Manvitha Ponnapati[SUP] 5 6 [/SUP], Christian Kramme[SUP] 7 8 [/SUP], Alexandru M Plesa[SUP] 7 8 [/SUP], George M Church[SUP] 7 8 [/SUP], Joseph M Jacobson[SUP] 5 6 [/SUP]
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.