Evidence map›Paper›PMID 34340537›Full record

ArticlemBio2021

Dynamics of SARS-CoV-2 Spike Proteins in Cell Entry: Control Elements in the Amino-Terminal Domains.

Enya Qing, Tom Kicmal, Binod Kumar, Grant M Hawkins, Emily Timm, Stanley Perlman, Tom Gallagher

Open access · goldAbstract read
In one paragraph

Article in mBio, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
4.0field-weighted citation impact, top 5% 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

52 citing papers in PubMed, 78 citations in OpenAlex.

  1. SARS-CoV-2 virus infection ofbioRxiv : the preprint server for biology · 2026
    Article
  2. Article
  3. Article
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  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Dynamic expedition of leading mutations in SARS-CoV-2 spike glycoproteins.Computational and structural biotechnology journal · 2024
    Article
  12. Article
  13. Article
  14. The accomplices: Heparan sulfates and N-glycans foster SARS-CoV-2 spike:ACE2 receptor binding and virus priming.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Adaptation of SARS-CoV-2 to ACE2Journal of virology · 2024
    Article
  20. Review
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

7 authors at 2 institutions in 1 country.

Enya QingDepartment of Microbiology and Immunology, Loyola University Chicagogrid.164971.c, Maywood, Illinois, USA.
Tom KicmalDepartment of Microbiology and Immunology, Loyola University Chicagogrid.164971.c, Maywood, Illinois, USA.
Binod KumarDepartment of Microbiology and Immunology, Loyola University Chicagogrid.164971.c, Maywood, Illinois, USA.
Grant M HawkinsDepartment of Microbiology and Immunology, Loyola University Chicagogrid.164971.c, Maywood, Illinois, USA.
Emily TimmDepartment of Microbiology and Immunology, Loyola University Chicagogrid.164971.c, Maywood, Illinois, USA.
Stanley PerlmanDepartment of Microbiology and Immunology, University of Iowagrid.214572.7, Iowa City, Iowa, USA.
Tom GallagherDepartment of Microbiology and Immunology, Loyola University Chicagogrid.164971.c, Maywood, Illinois, USA.
Loyola University Chicago · USUniversity of Iowa · US

Funding

SARS-CoV Proteins in Heterologous Viral InfectionP01AI060699 · NIAID · UNIVERSITY OF IOWA · PI PERLMAN, STANLEY · 2004 to 2021
$21.5M
HHS | National Institutes of Health (NIH) AI 060699NIAID NIH HHS P01 AI060699
6 · The paper itself

Abstract

Selective pressures drive adaptive changes in the coronavirus spike proteins directing virus-cell entry. These changes are concentrated in the amino-terminal domains (NTDs) and the receptor-binding domains (RBDs) of complex modular spike protein trimers. The impact of this hypervariability on virus entry is often unclear, particularly with respect to sarbecovirus NTD variations. Therefore, we constructed indels and substitutions within hypervariable NTD regions and used severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus-like particles and quantitative virus-cell entry assays to elucidate spike structures controlling this initial infection stage. We identified NTD variations that increased SARS-CoV-2 spike protein-mediated membrane fusion and cell entry. Increased cell entry correlated with greater presentation of RBDs to ACE2 receptors. This revealed a significant allosteric effect, in that changes within the NTDs can orient RBDs for effective virus-cell binding. Yet, those NTD changes elevating receptor binding and membrane fusion also reduced interdomain associations, leaving spikes on virus-like particles susceptible to irreversible inactivation. These findings parallel those obtained decades ago, in which comparisons of murine coronavirus spike protein variants established inverse relationships between membrane fusion potential and virus stability. Considerable hypervariability in the SARS-CoV-2 spike protein NTDs also appear to be driven by counterbalancing pressures for effective virus-cell entry and durable extracellular virus infectivity. These forces may selectively amplify SARS-CoV-2 variants of concern.

Indexed as

Virus InternalizationAngiotensin-Converting Enzyme 2Cell Line, TumorCOVID-19HEK293 CellsHeLa CellsHumansMembrane FusionProtein DomainsReceptors, VirusSARS-CoV-2Spike Glycoprotein, CoronavirusACE2 protein, humanAngiotensin-Converting Enzyme 2Receptors, VirusSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2coronaviruscoronavirus spike proteinmembrane fusionSARS-CoV-2virus entryvirus receptors

Identifiers

PMID34340537
PMCPMC8406164
OpenAlexW3187724905

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.