Evidence map›Paper›PMID 34352039›Full record

ArticlePLoS pathogens2021

Signatures in SARS-CoV-2 spike protein conferring escape to neutralizing antibodies.

Marta Alenquer, Filipe Ferreira, Diana Lousa, Mariana Valério, Mónica Medina-Lopes, Marie-Louise Bergman, Juliana Gonçalves, Jocelyne Demengeot, Ricardo B Leite, Jingtao Lilue and 5 more

Abstract read
In one paragraph

Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
–field-weighted citation impact
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

63 citing papers in PubMed.

  1. Article
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  7. Addressing pandemic-wide systematic errors in the SARS-CoV-2 phylogeny.bioRxiv : the preprint server for biology · 2024
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  8. Article
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  12. Review
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  14. Incipient functional SARS-CoV-2 diversification identified through neural network haplotype maps.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  15. Article
  16. Article
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  18. Article
  19. Article
  20. Article

3 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

15 authors.

Marta AlenquerCell Biology of Viral Infection Lab, Instituto Gulbenkian de Ciência; Oeiras, Portugal.
Filipe FerreiraCell Biology of Viral Infection Lab, Instituto Gulbenkian de Ciência; Oeiras, Portugal.
Diana LousaITQB NOVA, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa; Oeiras, Portugal.
Mariana ValérioITQB NOVA, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa; Oeiras, Portugal.ORCID 0000-0001-7340-0134
Mónica Medina-LopesCell Biology of Viral Infection Lab, Instituto Gulbenkian de Ciência; Oeiras, Portugal.
Marie-Louise BergmanLymphocyte Physiology Lab, Instituto Gulbenkian de Ciência; Oeiras, Portugal.ORCID 0000-0003-0691-4308
Juliana GonçalvesCEDOC NOVA, Centro de Estudos de Doenças Crónicas, Nova Medical School, Universidade Nova de Lisboa; Lisboa, Portugal.ORCID 0000-0002-1237-4152
Jocelyne DemengeotLymphocyte Physiology Lab, Instituto Gulbenkian de Ciência; Oeiras, Portugal.ORCID 0000-0002-4761-614X
Ricardo B LeiteGenomics Unit, Instituto Gulbenkian de Ciência; Oeiras, Portugal.ORCID 0000-0002-9622-3895
Jingtao LilueBioinformatics Unit, Instituto Gulbenkian de Ciência; Oeiras, Portugal.ORCID 0000-0002-1958-0231
Zemin NingThe Wellcome Trust Sanger Institute; Hinxton, United Kingdom.
Carlos Penha-GonçalvesDisease Genetics Lab, Instituto Gulbenkian de Ciência; Oeiras, Portugal.
Helena SoaresCEDOC NOVA, Centro de Estudos de Doenças Crónicas, Nova Medical School, Universidade Nova de Lisboa; Lisboa, Portugal.
Cláudio M SoaresITQB NOVA, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa; Oeiras, Portugal.ORCID 0000-0003-1154-556X
Maria João AmorimCell Biology of Viral Infection Lab, Instituto Gulbenkian de Ciência; Oeiras, Portugal.ORCID 0000-0002-4129-6659

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Understanding SARS-CoV-2 evolution and host immunity is critical to control COVID-19 pandemics. At the core is an arms-race between SARS-CoV-2 antibody and angiotensin-converting enzyme 2 (ACE2) recognition, a function of the viral protein spike. Mutations in spike impacting antibody and/or ACE2 binding are appearing worldwide, imposing the need to monitor SARS-CoV2 evolution and dynamics in the population. Determining signatures in SARS-CoV-2 that render the virus resistant to neutralizing antibodies is critical. We engineered 25 spike-pseudotyped lentiviruses containing individual and combined mutations in the spike protein, including all defining mutations in the variants of concern, to identify the effect of single and synergic amino acid substitutions in promoting immune escape. We confirmed that E484K evades antibody neutralization elicited by infection or vaccination, a capacity augmented when complemented by K417N and N501Y mutations. In silico analysis provided an explanation for E484K immune evasion. E484 frequently engages in interactions with antibodies but not with ACE2. Importantly, we identified a novel amino acid of concern, S494, which shares a similar pattern. Using the already circulating mutation S494P, we found that it reduces antibody neutralization of convalescent and post-immunization sera, particularly when combined with E484K and with mutations able to increase binding to ACE2, such as N501Y. Our analysis of synergic mutations provides a signature for hotspots for immune evasion and for targets of therapies, vaccines and diagnostics.

Indexed as

Amino Acid SubstitutionAngiotensin-Converting Enzyme 2Antibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralCell LineCOVID-19HumansImmune EvasionMutationProtein BindingSARS-CoV-2Spike Glycoprotein, CoronavirusAngiotensin-Converting Enzyme 2Antibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2

Identifiers

PMID34352039
PMCPMC8341613

What OpenQuestion holds

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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.