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

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 pla...

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Autores principales: Chatterjee, Pranam, Ponnapati, Manvitha, Kramme, Christian, Plesa, Alexandru M., Church, George M., Jacobson, Joseph M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683566/
https://www.ncbi.nlm.nih.gov/pubmed/33230174
http://dx.doi.org/10.1038/s42003-020-01470-7
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author Chatterjee, Pranam
Ponnapati, Manvitha
Kramme, Christian
Plesa, Alexandru M.
Church, George M.
Jacobson, Joseph M.
author_facet Chatterjee, Pranam
Ponnapati, Manvitha
Kramme, Christian
Plesa, Alexandru M.
Church, George M.
Jacobson, Joseph M.
author_sort Chatterjee, Pranam
collection PubMed
description 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.
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spelling pubmed-76835662020-12-03 Targeted intracellular degradation of SARS-CoV-2 via computationally optimized peptide fusions Chatterjee, Pranam Ponnapati, Manvitha Kramme, Christian Plesa, Alexandru M. Church, George M. Jacobson, Joseph M. Commun Biol Article 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. Nature Publishing Group UK 2020-11-23 /pmc/articles/PMC7683566/ /pubmed/33230174 http://dx.doi.org/10.1038/s42003-020-01470-7 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Chatterjee, Pranam
Ponnapati, Manvitha
Kramme, Christian
Plesa, Alexandru M.
Church, George M.
Jacobson, Joseph M.
Targeted intracellular degradation of SARS-CoV-2 via computationally optimized peptide fusions
title Targeted intracellular degradation of SARS-CoV-2 via computationally optimized peptide fusions
title_full Targeted intracellular degradation of SARS-CoV-2 via computationally optimized peptide fusions
title_fullStr Targeted intracellular degradation of SARS-CoV-2 via computationally optimized peptide fusions
title_full_unstemmed Targeted intracellular degradation of SARS-CoV-2 via computationally optimized peptide fusions
title_short Targeted intracellular degradation of SARS-CoV-2 via computationally optimized peptide fusions
title_sort targeted intracellular degradation of sars-cov-2 via computationally optimized peptide fusions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683566/
https://www.ncbi.nlm.nih.gov/pubmed/33230174
http://dx.doi.org/10.1038/s42003-020-01470-7
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