Effects of common mutations in the SARS-CoV-2 Spike RBD and its ligand, the human ACE2 receptor on binding affinity and kinetics

The interaction between the SARS-CoV-2 virus Spike protein receptor binding domain (RBD) and the ACE2 cell surface protein is required for viral infection of cells. Mutations in the RBD are present in SARS-CoV-2 variants of concern that have emerged independently worldwide. For example, the B.1.1.7...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Michael I Barton, Stuart A MacGowan, Mikhail A Kutuzov, Omer Dushek, Geoffrey John Barton, P Anton van der Merwe
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	COVID-19 SARS-CoV-2 ACE2 viral receptor affinity coronavirus Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6de5dd278c3443c5b73c853e319f1f0e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6de5dd278c3443c5b73c853e319f1f0e
record_format	dspace
spelling	oai:doaj.org-article:6de5dd278c3443c5b73c853e319f1f0e2021-12-01T12:14:34ZEffects of common mutations in the SARS-CoV-2 Spike RBD and its ligand, the human ACE2 receptor on binding affinity and kinetics10.7554/eLife.706582050-084Xe70658https://doaj.org/article/6de5dd278c3443c5b73c853e319f1f0e2021-08-01T00:00:00Zhttps://elifesciences.org/articles/70658https://doaj.org/toc/2050-084XThe interaction between the SARS-CoV-2 virus Spike protein receptor binding domain (RBD) and the ACE2 cell surface protein is required for viral infection of cells. Mutations in the RBD are present in SARS-CoV-2 variants of concern that have emerged independently worldwide. For example, the B.1.1.7 lineage has a mutation (N501Y) in its Spike RBD that enhances binding to ACE2. There are also ACE2 alleles in humans with mutations in the RBD binding site. Here we perform a detailed affinity and kinetics analysis of the effect of five common RBD mutations (K417N, K417T, N501Y, E484K, and S477N) and two common ACE2 mutations (S19P and K26R) on the RBD/ACE2 interaction. We analysed the effects of individual RBD mutations and combinations found in new SARS-CoV-2 Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P1) variants. Most of these mutations increased the affinity of the RBD/ACE2 interaction. The exceptions were mutations K417N/T, which decreased the affinity. Taken together with other studies, our results suggest that the N501Y and S477N mutations enhance transmission primarily by enhancing binding, the K417N/T mutations facilitate immune escape, and the E484K mutation enhances binding and immune escape.Michael I BartonStuart A MacGowanMikhail A KutuzovOmer DushekGeoffrey John BartonP Anton van der MerweeLife Sciences Publications LtdarticleCOVID-19SARS-CoV-2ACE2viral receptoraffinitycoronavirusMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	COVID-19 SARS-CoV-2 ACE2 viral receptor affinity coronavirus Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	COVID-19 SARS-CoV-2 ACE2 viral receptor affinity coronavirus Medicine R Science Q Biology (General) QH301-705.5 Michael I Barton Stuart A MacGowan Mikhail A Kutuzov Omer Dushek Geoffrey John Barton P Anton van der Merwe Effects of common mutations in the SARS-CoV-2 Spike RBD and its ligand, the human ACE2 receptor on binding affinity and kinetics
description	The interaction between the SARS-CoV-2 virus Spike protein receptor binding domain (RBD) and the ACE2 cell surface protein is required for viral infection of cells. Mutations in the RBD are present in SARS-CoV-2 variants of concern that have emerged independently worldwide. For example, the B.1.1.7 lineage has a mutation (N501Y) in its Spike RBD that enhances binding to ACE2. There are also ACE2 alleles in humans with mutations in the RBD binding site. Here we perform a detailed affinity and kinetics analysis of the effect of five common RBD mutations (K417N, K417T, N501Y, E484K, and S477N) and two common ACE2 mutations (S19P and K26R) on the RBD/ACE2 interaction. We analysed the effects of individual RBD mutations and combinations found in new SARS-CoV-2 Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P1) variants. Most of these mutations increased the affinity of the RBD/ACE2 interaction. The exceptions were mutations K417N/T, which decreased the affinity. Taken together with other studies, our results suggest that the N501Y and S477N mutations enhance transmission primarily by enhancing binding, the K417N/T mutations facilitate immune escape, and the E484K mutation enhances binding and immune escape.
format	article
author	Michael I Barton Stuart A MacGowan Mikhail A Kutuzov Omer Dushek Geoffrey John Barton P Anton van der Merwe
author_facet	Michael I Barton Stuart A MacGowan Mikhail A Kutuzov Omer Dushek Geoffrey John Barton P Anton van der Merwe
author_sort	Michael I Barton
title	Effects of common mutations in the SARS-CoV-2 Spike RBD and its ligand, the human ACE2 receptor on binding affinity and kinetics
title_short	Effects of common mutations in the SARS-CoV-2 Spike RBD and its ligand, the human ACE2 receptor on binding affinity and kinetics
title_full	Effects of common mutations in the SARS-CoV-2 Spike RBD and its ligand, the human ACE2 receptor on binding affinity and kinetics
title_fullStr	Effects of common mutations in the SARS-CoV-2 Spike RBD and its ligand, the human ACE2 receptor on binding affinity and kinetics
title_full_unstemmed	Effects of common mutations in the SARS-CoV-2 Spike RBD and its ligand, the human ACE2 receptor on binding affinity and kinetics
title_sort	effects of common mutations in the sars-cov-2 spike rbd and its ligand, the human ace2 receptor on binding affinity and kinetics
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/6de5dd278c3443c5b73c853e319f1f0e
work_keys_str_mv	AT michaelibarton effectsofcommonmutationsinthesarscov2spikerbdanditsligandthehumanace2receptoronbindingaffinityandkinetics AT stuartamacgowan effectsofcommonmutationsinthesarscov2spikerbdanditsligandthehumanace2receptoronbindingaffinityandkinetics AT mikhailakutuzov effectsofcommonmutationsinthesarscov2spikerbdanditsligandthehumanace2receptoronbindingaffinityandkinetics AT omerdushek effectsofcommonmutationsinthesarscov2spikerbdanditsligandthehumanace2receptoronbindingaffinityandkinetics AT geoffreyjohnbarton effectsofcommonmutationsinthesarscov2spikerbdanditsligandthehumanace2receptoronbindingaffinityandkinetics AT pantonvandermerwe effectsofcommonmutationsinthesarscov2spikerbdanditsligandthehumanace2receptoronbindingaffinityandkinetics
_version_	1718405179028537344

Effects of common mutations in the SARS-CoV-2 Spike RBD and its ligand, the human ACE2 receptor on binding affinity and kinetics

Ejemplares similares