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Multivalent 9-O-Acetylated-sialic acid glycoclusters as potent inhibitors for SARS-CoV-2 infection
The recent emergence of highly transmissible SARS-CoV-2 variants illustrates the urgent need to better understand the molecular details of the virus binding to its host cell and to develop anti-viral strategies. While many studies focused on the role of the angiotensin-converting enzyme 2 receptor i...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091252/ https://www.ncbi.nlm.nih.gov/pubmed/35538121 http://dx.doi.org/10.1038/s41467-022-30313-8 |
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author | Petitjean, Simon J. L. Chen, Wenzhang Koehler, Melanie Jimmidi, Ravikumar Yang, Jinsung Mohammed, Danahe Juniku, Blinera Stanifer, Megan L. Boulant, Steeve Vincent, Stéphane P. Alsteens, David |
author_facet | Petitjean, Simon J. L. Chen, Wenzhang Koehler, Melanie Jimmidi, Ravikumar Yang, Jinsung Mohammed, Danahe Juniku, Blinera Stanifer, Megan L. Boulant, Steeve Vincent, Stéphane P. Alsteens, David |
author_sort | Petitjean, Simon J. L. |
collection | PubMed |
description | The recent emergence of highly transmissible SARS-CoV-2 variants illustrates the urgent need to better understand the molecular details of the virus binding to its host cell and to develop anti-viral strategies. While many studies focused on the role of the angiotensin-converting enzyme 2 receptor in the infection, others suggest the important role of cell attachment factors such as glycans. Here, we use atomic force microscopy to study these early binding events with the focus on the role of sialic acids (SA). We show that SARS-CoV-2 binds specifically to 9-O-acetylated-SA with a moderate affinity, supporting its role as an attachment factor during virus landing to cell host surfaces. For therapeutic purposes and based on this finding, we have designed novel blocking molecules with various topologies and carrying a controlled number of SA residues, enhancing affinity through a multivalent effect. Inhibition assays show that the AcSA-derived glycoclusters are potent inhibitors of cell binding and infectivity, offering new perspectives in the treatment of SARS-CoV-2 infection. |
format | Online Article Text |
id | pubmed-9091252 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-90912522022-05-12 Multivalent 9-O-Acetylated-sialic acid glycoclusters as potent inhibitors for SARS-CoV-2 infection Petitjean, Simon J. L. Chen, Wenzhang Koehler, Melanie Jimmidi, Ravikumar Yang, Jinsung Mohammed, Danahe Juniku, Blinera Stanifer, Megan L. Boulant, Steeve Vincent, Stéphane P. Alsteens, David Nat Commun Article The recent emergence of highly transmissible SARS-CoV-2 variants illustrates the urgent need to better understand the molecular details of the virus binding to its host cell and to develop anti-viral strategies. While many studies focused on the role of the angiotensin-converting enzyme 2 receptor in the infection, others suggest the important role of cell attachment factors such as glycans. Here, we use atomic force microscopy to study these early binding events with the focus on the role of sialic acids (SA). We show that SARS-CoV-2 binds specifically to 9-O-acetylated-SA with a moderate affinity, supporting its role as an attachment factor during virus landing to cell host surfaces. For therapeutic purposes and based on this finding, we have designed novel blocking molecules with various topologies and carrying a controlled number of SA residues, enhancing affinity through a multivalent effect. Inhibition assays show that the AcSA-derived glycoclusters are potent inhibitors of cell binding and infectivity, offering new perspectives in the treatment of SARS-CoV-2 infection. Nature Publishing Group UK 2022-05-10 /pmc/articles/PMC9091252/ /pubmed/35538121 http://dx.doi.org/10.1038/s41467-022-30313-8 Text en © The Author(s) 2022, corrected publication 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Petitjean, Simon J. L. Chen, Wenzhang Koehler, Melanie Jimmidi, Ravikumar Yang, Jinsung Mohammed, Danahe Juniku, Blinera Stanifer, Megan L. Boulant, Steeve Vincent, Stéphane P. Alsteens, David Multivalent 9-O-Acetylated-sialic acid glycoclusters as potent inhibitors for SARS-CoV-2 infection |
title | Multivalent 9-O-Acetylated-sialic acid glycoclusters as potent inhibitors for SARS-CoV-2 infection |
title_full | Multivalent 9-O-Acetylated-sialic acid glycoclusters as potent inhibitors for SARS-CoV-2 infection |
title_fullStr | Multivalent 9-O-Acetylated-sialic acid glycoclusters as potent inhibitors for SARS-CoV-2 infection |
title_full_unstemmed | Multivalent 9-O-Acetylated-sialic acid glycoclusters as potent inhibitors for SARS-CoV-2 infection |
title_short | Multivalent 9-O-Acetylated-sialic acid glycoclusters as potent inhibitors for SARS-CoV-2 infection |
title_sort | multivalent 9-o-acetylated-sialic acid glycoclusters as potent inhibitors for sars-cov-2 infection |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091252/ https://www.ncbi.nlm.nih.gov/pubmed/35538121 http://dx.doi.org/10.1038/s41467-022-30313-8 |
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