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The free fatty acid–binding pocket is a conserved hallmark in pathogenic β-coronavirus spike proteins from SARS-CoV to Omicron
As coronavirus disease 2019 (COVID-19) persists, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) emerge, accumulating spike (S) glycoprotein mutations. S receptor binding domain (RBD) comprises a free fatty acid (FFA)–binding pocket. FFA binding stabilizes a l...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Association for the Advancement of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9683698/ https://www.ncbi.nlm.nih.gov/pubmed/36417532 http://dx.doi.org/10.1126/sciadv.adc9179 |
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author | Toelzer, Christine Gupta, Kapil Yadav, Sathish K. N. Hodgson, Lorna Williamson, Maia Kavanagh Buzas, Dora Borucu, Ufuk Powers, Kyle Stenner, Richard Vasileiou, Kate Garzoni, Frederic Fitzgerald, Daniel Payré, Christine Gautam, Gunjan Lambeau, Gérard Davidson, Andrew D. Verkade, Paul Frank, Martin Berger, Imre Schaffitzel, Christiane |
author_facet | Toelzer, Christine Gupta, Kapil Yadav, Sathish K. N. Hodgson, Lorna Williamson, Maia Kavanagh Buzas, Dora Borucu, Ufuk Powers, Kyle Stenner, Richard Vasileiou, Kate Garzoni, Frederic Fitzgerald, Daniel Payré, Christine Gautam, Gunjan Lambeau, Gérard Davidson, Andrew D. Verkade, Paul Frank, Martin Berger, Imre Schaffitzel, Christiane |
author_sort | Toelzer, Christine |
collection | PubMed |
description | As coronavirus disease 2019 (COVID-19) persists, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) emerge, accumulating spike (S) glycoprotein mutations. S receptor binding domain (RBD) comprises a free fatty acid (FFA)–binding pocket. FFA binding stabilizes a locked S conformation, interfering with virus infectivity. We provide evidence that the pocket is conserved in pathogenic β-coronaviruses (β-CoVs) infecting humans. SARS-CoV, MERS-CoV, SARS-CoV-2, and VOCs bind the essential FFA linoleic acid (LA), while binding is abolished by one mutation in common cold–causing HCoV-HKU1. In the SARS-CoV S structure, LA stabilizes the locked conformation, while the open, infectious conformation is devoid of LA. Electron tomography of SARS-CoV-2–infected cells reveals that LA treatment inhibits viral replication, resulting in fewer deformed virions. Our results establish FFA binding as a hallmark of pathogenic β-CoV infection and replication, setting the stage for FFA-based antiviral strategies to overcome COVID-19. |
format | Online Article Text |
id | pubmed-9683698 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-96836982022-12-05 The free fatty acid–binding pocket is a conserved hallmark in pathogenic β-coronavirus spike proteins from SARS-CoV to Omicron Toelzer, Christine Gupta, Kapil Yadav, Sathish K. N. Hodgson, Lorna Williamson, Maia Kavanagh Buzas, Dora Borucu, Ufuk Powers, Kyle Stenner, Richard Vasileiou, Kate Garzoni, Frederic Fitzgerald, Daniel Payré, Christine Gautam, Gunjan Lambeau, Gérard Davidson, Andrew D. Verkade, Paul Frank, Martin Berger, Imre Schaffitzel, Christiane Sci Adv Biomedicine and Life Sciences As coronavirus disease 2019 (COVID-19) persists, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) emerge, accumulating spike (S) glycoprotein mutations. S receptor binding domain (RBD) comprises a free fatty acid (FFA)–binding pocket. FFA binding stabilizes a locked S conformation, interfering with virus infectivity. We provide evidence that the pocket is conserved in pathogenic β-coronaviruses (β-CoVs) infecting humans. SARS-CoV, MERS-CoV, SARS-CoV-2, and VOCs bind the essential FFA linoleic acid (LA), while binding is abolished by one mutation in common cold–causing HCoV-HKU1. In the SARS-CoV S structure, LA stabilizes the locked conformation, while the open, infectious conformation is devoid of LA. Electron tomography of SARS-CoV-2–infected cells reveals that LA treatment inhibits viral replication, resulting in fewer deformed virions. Our results establish FFA binding as a hallmark of pathogenic β-CoV infection and replication, setting the stage for FFA-based antiviral strategies to overcome COVID-19. American Association for the Advancement of Science 2022-11-23 /pmc/articles/PMC9683698/ /pubmed/36417532 http://dx.doi.org/10.1126/sciadv.adc9179 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Toelzer, Christine Gupta, Kapil Yadav, Sathish K. N. Hodgson, Lorna Williamson, Maia Kavanagh Buzas, Dora Borucu, Ufuk Powers, Kyle Stenner, Richard Vasileiou, Kate Garzoni, Frederic Fitzgerald, Daniel Payré, Christine Gautam, Gunjan Lambeau, Gérard Davidson, Andrew D. Verkade, Paul Frank, Martin Berger, Imre Schaffitzel, Christiane The free fatty acid–binding pocket is a conserved hallmark in pathogenic β-coronavirus spike proteins from SARS-CoV to Omicron |
title | The free fatty acid–binding pocket is a conserved hallmark in pathogenic β-coronavirus spike proteins from SARS-CoV to Omicron |
title_full | The free fatty acid–binding pocket is a conserved hallmark in pathogenic β-coronavirus spike proteins from SARS-CoV to Omicron |
title_fullStr | The free fatty acid–binding pocket is a conserved hallmark in pathogenic β-coronavirus spike proteins from SARS-CoV to Omicron |
title_full_unstemmed | The free fatty acid–binding pocket is a conserved hallmark in pathogenic β-coronavirus spike proteins from SARS-CoV to Omicron |
title_short | The free fatty acid–binding pocket is a conserved hallmark in pathogenic β-coronavirus spike proteins from SARS-CoV to Omicron |
title_sort | free fatty acid–binding pocket is a conserved hallmark in pathogenic β-coronavirus spike proteins from sars-cov to omicron |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9683698/ https://www.ncbi.nlm.nih.gov/pubmed/36417532 http://dx.doi.org/10.1126/sciadv.adc9179 |
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