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Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution

SARS-CoV-2 has evolved variants with substitutions in the spike receptor-binding domain (RBD) that impact its affinity for ACE2 receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites—a phenomenon called epis...

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Autores principales: Starr, Tyler N., Greaney, Allison J., Hannon, William W., Loes, Andrea N., Hauser, Kevin, Dillen, Josh R., Ferri, Elena, Farrell, Ariana Ghez, Dadonaite, Bernadeta, McCallum, Matthew, Matreyek, Kenneth A., Corti, Davide, Veesler, David, Snell, Gyorgy, Bloom, Jesse D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273037/
https://www.ncbi.nlm.nih.gov/pubmed/35762884
http://dx.doi.org/10.1126/science.abo7896
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author Starr, Tyler N.
Greaney, Allison J.
Hannon, William W.
Loes, Andrea N.
Hauser, Kevin
Dillen, Josh R.
Ferri, Elena
Farrell, Ariana Ghez
Dadonaite, Bernadeta
McCallum, Matthew
Matreyek, Kenneth A.
Corti, Davide
Veesler, David
Snell, Gyorgy
Bloom, Jesse D.
author_facet Starr, Tyler N.
Greaney, Allison J.
Hannon, William W.
Loes, Andrea N.
Hauser, Kevin
Dillen, Josh R.
Ferri, Elena
Farrell, Ariana Ghez
Dadonaite, Bernadeta
McCallum, Matthew
Matreyek, Kenneth A.
Corti, Davide
Veesler, David
Snell, Gyorgy
Bloom, Jesse D.
author_sort Starr, Tyler N.
collection PubMed
description SARS-CoV-2 has evolved variants with substitutions in the spike receptor-binding domain (RBD) that impact its affinity for ACE2 receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites—a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure the effects on ACE2 binding of all single amino-acid mutations in the Wuhan-Hu-1, Alpha, Beta, Delta, and Eta variant RBDs. Some substitutions, most prominently N501Y, cause epistatic shifts in the effects of mutations at other sites. These epistatic shifts shape subsequent evolutionary change, for example enabling many of the antibody-escape substitutions in the Omicron RBD. These epistatic shifts occur despite high conservation of the overall RBD structure. Our data shed light on RBD sequence-function relationships and facilitate interpretation of ongoing SARS-CoV-2 evolution.
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spelling pubmed-92730372022-07-14 Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution Starr, Tyler N. Greaney, Allison J. Hannon, William W. Loes, Andrea N. Hauser, Kevin Dillen, Josh R. Ferri, Elena Farrell, Ariana Ghez Dadonaite, Bernadeta McCallum, Matthew Matreyek, Kenneth A. Corti, Davide Veesler, David Snell, Gyorgy Bloom, Jesse D. Science Reports SARS-CoV-2 has evolved variants with substitutions in the spike receptor-binding domain (RBD) that impact its affinity for ACE2 receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites—a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure the effects on ACE2 binding of all single amino-acid mutations in the Wuhan-Hu-1, Alpha, Beta, Delta, and Eta variant RBDs. Some substitutions, most prominently N501Y, cause epistatic shifts in the effects of mutations at other sites. These epistatic shifts shape subsequent evolutionary change, for example enabling many of the antibody-escape substitutions in the Omicron RBD. These epistatic shifts occur despite high conservation of the overall RBD structure. Our data shed light on RBD sequence-function relationships and facilitate interpretation of ongoing SARS-CoV-2 evolution. American Association for the Advancement of Science 2022-06-28 /pmc/articles/PMC9273037/ /pubmed/35762884 http://dx.doi.org/10.1126/science.abo7896 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 Reports
Starr, Tyler N.
Greaney, Allison J.
Hannon, William W.
Loes, Andrea N.
Hauser, Kevin
Dillen, Josh R.
Ferri, Elena
Farrell, Ariana Ghez
Dadonaite, Bernadeta
McCallum, Matthew
Matreyek, Kenneth A.
Corti, Davide
Veesler, David
Snell, Gyorgy
Bloom, Jesse D.
Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution
title Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution
title_full Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution
title_fullStr Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution
title_full_unstemmed Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution
title_short Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution
title_sort shifting mutational constraints in the sars-cov-2 receptor-binding domain during viral evolution
topic Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273037/
https://www.ncbi.nlm.nih.gov/pubmed/35762884
http://dx.doi.org/10.1126/science.abo7896
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