Evidence map›Paper›PMID 34200372›Full record

ArticleCells2021

ACE2-Independent Interaction of SARS-CoV-2 Spike Protein with Human Epithelial Cells Is Inhibited by Unfractionated Heparin.

Lynda J Partridge, Lucy Urwin, Martin J H Nicklin, David C James, Luke R Green, Peter N Monk

Open access · goldAbstract read
In one paragraph

Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
3.8field-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

45 citing papers in PubMed, 71 citations in OpenAlex.

  1. Review
  2. Proteomic Analysis of COVID-19 Infection.Advances in experimental medicine and biology · 2026
    Article
  3. Molecular mechanisms of SARS-CoV-2 entry: implications for biomedical strategies.Microbiology and molecular biology reviews : MMBR · 2025
    Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
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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 1 institution in 1 country.

Lynda J PartridgeDepartment of Molecular Biology and Biotechnology, The University of Sheffield, Sheffield S10 2TN, UK.
Lucy UrwinDepartment of Infection, Immunity and Cardiovascular Disease, The University of Sheffield, Sheffield S10 2RX, UK.ORCID 0000-0002-7667-8630
Martin J H NicklinDepartment of Infection, Immunity and Cardiovascular Disease, The University of Sheffield, Sheffield S10 2RX, UK.
David C JamesDepartment of Chemical and Biological Engineering, The University of Sheffield, Sheffield S1 4NL, UK.
Luke R GreenDepartment of Infection, Immunity and Cardiovascular Disease, The University of Sheffield, Sheffield S10 2RX, UK.ORCID 0000-0002-2836-2041
Peter N MonkDepartment of Infection, Immunity and Cardiovascular Disease, The University of Sheffield, Sheffield S10 2RX, UK.ORCID 0000-0003-4637-3059
University of Sheffield · GB

Funding

Medical Research Council MR/S004688/1
6 · The paper itself

Abstract

Coronaviruses such as SARS-CoV-2, which is responsible for COVID-19, depend on virus spike protein binding to host cell receptors to cause infection. The SARS-CoV-2 spike protein binds primarily to ACE2 on target cells and is then processed by membrane proteases, including TMPRSS2, leading to viral internalisation or fusion with the plasma membrane. It has been suggested, however, that receptors other than ACE2 may be involved in virus binding. We have investigated the interactions of recombinant versions of the spike protein with human epithelial cell lines that express low/very low levels of ACE2 and TMPRSS2 in a proxy assay for interaction with host cells. A tagged form of the spike protein containing the S1 and S2 regions bound in a temperature-dependent manner to all cell lines, whereas the S1 region alone and the receptor-binding domain (RBD) interacted only weakly. Spike protein associated with cells independently of ACE2 and TMPRSS2, while RBD required the presence of high levels of ACE2 for interaction. As the spike protein has previously been shown to bind heparin, a soluble glycosaminoglycan, we tested the effects of various heparins on ACE2-independent spike protein interaction with cells. Unfractionated heparin inhibited spike protein interaction with an IC

Indexed as

A549 CellsAngiotensin-Converting Enzyme 2AnimalsBinding SitesCaco-2 CellsCell LineChlorocebus aethiopsDermatan SulfateDown-RegulationEpithelial CellsGlycosaminoglycansHaCaT CellsHEK293 CellsHeparan SulfateHeparinHumansACE2 protein, humanAngiotensin-Converting Enzyme 2Dermatan SulfateGlycosaminoglycansHeparan SulfateHeparinSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2glycosaminoglycanheparinSARS-CoV-2spike protein

Identifiers

PMID34200372
PMCPMC8229176
OpenAlexW3168333544

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.