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Antiviral Activity against SARS-CoV-2 of Conformationally Constrained Helical Peptides Derived from Angiotensin-Converting Enzyme 2
[Image: see text] Despite the availability of vaccines, COVID-19 continues to be aggressive, especially in immunocompromised individuals. Therefore, the development of a specific therapeutic agent with antiviral activity against SARS-CoV-2 is necessary. The infection pathway starts when the receptor...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10275481/ https://www.ncbi.nlm.nih.gov/pubmed/37387789 http://dx.doi.org/10.1021/acsomega.3c01436 |
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author | Quagliata, Michael Stincarelli, Maria Alfreda Papini, Anna Maria Giannecchini, Simone Rovero, Paolo |
author_facet | Quagliata, Michael Stincarelli, Maria Alfreda Papini, Anna Maria Giannecchini, Simone Rovero, Paolo |
author_sort | Quagliata, Michael |
collection | PubMed |
description | [Image: see text] Despite the availability of vaccines, COVID-19 continues to be aggressive, especially in immunocompromised individuals. Therefore, the development of a specific therapeutic agent with antiviral activity against SARS-CoV-2 is necessary. The infection pathway starts when the receptor binding domain of the viral spike protein interacts with the angiotensin converting enzyme 2 (ACE2), which acts as a host receptor for the RBD expressed on the host cell surface. In this scenario, ACE2 analogs binding to the RBD and preventing the cell entry can be promising antiviral agents. Most of the ACE2 residues involved in the interaction belong to the α1 helix, more specifically to the minimal fragment ACE2(24–42). In order to increase the stability of the secondary structure and thus antiviral activity, we designed different triazole-stapled analogs, changing the position and the number of bridges. The peptide called P3, which has the triazole-containing bridge in the positions 36–40, showed promising antiviral activity at micromolar concentrations assessed by plaque reduction assay. On the other hand, the double-stapled peptide P4 lost the activity, showing that excessive rigidity disfavors the interaction with the RBD. |
format | Online Article Text |
id | pubmed-10275481 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-102754812023-06-16 Antiviral Activity against SARS-CoV-2 of Conformationally Constrained Helical Peptides Derived from Angiotensin-Converting Enzyme 2 Quagliata, Michael Stincarelli, Maria Alfreda Papini, Anna Maria Giannecchini, Simone Rovero, Paolo ACS Omega [Image: see text] Despite the availability of vaccines, COVID-19 continues to be aggressive, especially in immunocompromised individuals. Therefore, the development of a specific therapeutic agent with antiviral activity against SARS-CoV-2 is necessary. The infection pathway starts when the receptor binding domain of the viral spike protein interacts with the angiotensin converting enzyme 2 (ACE2), which acts as a host receptor for the RBD expressed on the host cell surface. In this scenario, ACE2 analogs binding to the RBD and preventing the cell entry can be promising antiviral agents. Most of the ACE2 residues involved in the interaction belong to the α1 helix, more specifically to the minimal fragment ACE2(24–42). In order to increase the stability of the secondary structure and thus antiviral activity, we designed different triazole-stapled analogs, changing the position and the number of bridges. The peptide called P3, which has the triazole-containing bridge in the positions 36–40, showed promising antiviral activity at micromolar concentrations assessed by plaque reduction assay. On the other hand, the double-stapled peptide P4 lost the activity, showing that excessive rigidity disfavors the interaction with the RBD. American Chemical Society 2023-06-13 /pmc/articles/PMC10275481/ /pubmed/37387789 http://dx.doi.org/10.1021/acsomega.3c01436 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Quagliata, Michael Stincarelli, Maria Alfreda Papini, Anna Maria Giannecchini, Simone Rovero, Paolo Antiviral Activity against SARS-CoV-2 of Conformationally Constrained Helical Peptides Derived from Angiotensin-Converting Enzyme 2 |
title | Antiviral Activity
against SARS-CoV-2 of Conformationally
Constrained Helical Peptides Derived from Angiotensin-Converting Enzyme
2 |
title_full | Antiviral Activity
against SARS-CoV-2 of Conformationally
Constrained Helical Peptides Derived from Angiotensin-Converting Enzyme
2 |
title_fullStr | Antiviral Activity
against SARS-CoV-2 of Conformationally
Constrained Helical Peptides Derived from Angiotensin-Converting Enzyme
2 |
title_full_unstemmed | Antiviral Activity
against SARS-CoV-2 of Conformationally
Constrained Helical Peptides Derived from Angiotensin-Converting Enzyme
2 |
title_short | Antiviral Activity
against SARS-CoV-2 of Conformationally
Constrained Helical Peptides Derived from Angiotensin-Converting Enzyme
2 |
title_sort | antiviral activity
against sars-cov-2 of conformationally
constrained helical peptides derived from angiotensin-converting enzyme
2 |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10275481/ https://www.ncbi.nlm.nih.gov/pubmed/37387789 http://dx.doi.org/10.1021/acsomega.3c01436 |
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