Evidence map›Paper›PMID 34435953›Full record

ArticleeLife2021

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

Michael I Barton, Stuart A MacGowan, Mikhail A Kutuzov, Omer Dushek, Geoffrey John Barton, P Anton van der Merwe

Open access · goldAbstract read
In one paragraph

Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 236 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
236citing papers in PubMed, 1 pooled it
21.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

236 citing papers in PubMed, 1 synthesis or guideline pooled it, 376 citations in OpenAlex.

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176 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Michael I Barton *Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.ORCID 0000-0002-9263-6481
Stuart A MacGowan *School of Life Sciences, University of Dundee, Dundee, United Kingdom.ORCID 0000-0003-4233-5071
Mikhail A KutuzovSir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.ORCID 0000-0003-3386-4350
Omer DushekSir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.ORCID 0000-0001-5847-5226
Geoffrey John BartonSchool of Life Sciences, University of Dundee, Dundee, United Kingdom.ORCID 0000-0002-9014-5355
P Anton van der MerweSir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.ORCID 0000-0001-9902-6590
University of Oxford · GBUniversity of Dundee · GBErasmus MC · NL

Funding

Biotechnology and Biological Sciences Research Council BB/G022682/1Biotechnology and Biological Sciences Research Council BB/J019364/1Biotechnology and Biological Sciences Research Council BB/L020742/1Biotechnology and Biological Sciences Research Council BB/R014752/1Wellcome TrustWellcome Trust 101651/Z/13/Z).Wellcome Trust 207537/Z/17/Z828
6 · The paper itself

Abstract

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.

Indexed as

MutationAngiotensin-Converting Enzyme 2Binding SitesCOVID-19HumansKineticsLigandsMolecular Dynamics SimulationProtein BindingProtein DomainsProtein Interaction Domains and MotifsSARS-CoV-2Spike Glycoprotein, CoronavirusACE2 protein, humanAngiotensin-Converting Enzyme 2LigandsSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2ACE2affinitybiochemistrychemical biologycoronavirusCOVID-19humaninfectious diseasemicrobiologySARS-CoV-2viral receptor

Identifiers

PMID34435953
PMCPMC8480977
OpenAlexW3193526107

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.