Evidence map›Paper›PMID 33125711›Full record

ArticleBritish journal of pharmacology2021

Unfractionated heparin inhibits live wild type SARS-CoV-2 cell infectivity at therapeutically relevant concentrations.

Julia A Tree, Jeremy E Turnbull, Karen R Buttigieg, Michael J Elmore, Naomi Coombes, John Hogwood, Courtney J Mycroft-West, Marcelo A Lima, Mark A Skidmore, Richard Karlsson and 10 more

Open access · hybridAbstract read
In one paragraph

Article in British journal of pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
2.0field-weighted citation impact, top 7% 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

68 citing papers in PubMed, 96 citations in OpenAlex.

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  10. 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
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  17. Non-anticoagulant heparin derivatives for COVID-19 treatment.International journal of biological macromolecules · 2023
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8 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

20 authors at 10 institutions in 2 countries.

Julia A TreeNational Infection Service, Public Health England, Porton Down, Salisbury, UK.
Jeremy E TurnbullDepartment of Biochemistry and Systems Biology, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool, UK.
Karen R ButtigiegNational Infection Service, Public Health England, Porton Down, Salisbury, UK.
Michael J ElmoreNational Infection Service, Public Health England, Porton Down, Salisbury, UK.
Naomi CoombesNational Infection Service, Public Health England, Porton Down, Salisbury, UK.
John HogwoodHaemostasis Section, Biotherapeutics, National Institute for Biological Standards and Control (NIBSC), Potters Bar, UK.
Courtney J Mycroft-WestMolecular & Structural Biosciences, School of Life Sciences, Keele University, Newcastle-Under-Lyme, UK.
Marcelo A LimaMolecular & Structural Biosciences, School of Life Sciences, Keele University, Newcastle-Under-Lyme, UK.
Mark A SkidmoreMolecular & Structural Biosciences, School of Life Sciences, Keele University, Newcastle-Under-Lyme, UK.
Richard KarlssonCopenhagen Center for Glycomics, Department of Cellular & Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
Yen-Hsi ChenCopenhagen Center for Glycomics, Department of Cellular & Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
Zhang YangCopenhagen Center for Glycomics, Department of Cellular & Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
Cosma Mirella SpallutoDepartment of Respiratory Medicine, University of Southampton, Southampton, UK.
Karl J StaplesDepartment of Respiratory Medicine, University of Southampton, Southampton, UK.
Edwin A YatesDepartment of Biochemistry and Systems Biology, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool, UK.
Elaine GrayHaemostasis Section, Biotherapeutics, National Institute for Biological Standards and Control (NIBSC), Potters Bar, UK.
Dave SinghMedicines Evaluation Unit, University of Manchester, Manchester University Hospital NHS Foundation Trust, Manchester, UK.
Tom WilkinsonDepartment of Respiratory Medicine, University of Southampton, Southampton, UK.
Clive P PageSackler Institute of Pulmonary Pharmacology, King's College London, London, UK.
Miles W CarrollNational Infection Service, Public Health England, Porton Down, Salisbury, UK.
Public Health England · GBKeele University · GBUniversity of Copenhagen · DKKing's College London · GBUniversity of Liverpool · GBUniversity of Southampton · GBCentre for Human Genetics · GBNational Institute for Biological Standards and Control · GBNIHR Southampton Respiratory Biomedical Research Unit · GBUniversity of Manchester · GB

Funding

Medical Research Council G0700852Public Health EnglandUniversity of KeeleUniversity of Liverpool
6 · The paper itself

Abstract

background and purposeCurrently, there are no licensed vaccines and limited antivirals for the treatment of COVID-19. Heparin (delivered systemically) is currently used to treat anticoagulant anomalies in COVID-19 patients. Additionally, in the United Kingdom, Brazil and Australia, nebulised unfractionated heparin (UFH) is being trialled in COVID-19 patients as a potential treatment. A systematic comparison of the potential antiviral effect of various heparin preparations on live wild type SARS-CoV-2, in vitro, is needed. EXPERIMENTAL APPROACH: Seven different heparin preparations including UFH and low MW heparins (LMWH) of porcine or bovine origin were screened for antiviral activity against live SARS-CoV-2 (Australia/VIC01/2020) using a plaque inhibition assay with Vero E6 cells. Interaction of heparin with spike protein RBD was studied using differential scanning fluorimetry and the inhibition of RBD binding to human ACE2 protein using elisa assays was examined. KEY

resultsAll the UFH preparations had potent antiviral effects, with IC CONCLUSION AND IMPLICATIONS: This comparison of clinically relevant heparins shows that UFH has significantly stronger SARS-CoV-2 antiviral activity compared to LMWHs. UFH acts to directly inhibit binding of spike protein to the human ACE2 protein receptor. Overall, the data strongly support further clinical investigation of UFH as a potential treatment for patients with COVID-19.

Indexed as

Angiotensin-Converting Enzyme 2AnimalsAntiviral AgentsChlorocebus aethiopsCOVID-19 Drug TreatmentHeparinHeparin, Low-Molecular-WeightProtein BindingSARS-CoV-2Spike Glycoprotein, CoronavirusViral Plaque AssayAngiotensin-Converting Enzyme 2Antiviral AgentsHeparinHeparin, Low-Molecular-WeightSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2COVID-19heparinLMWHnebulisedSARS-CoV-2UFH

Identifiers

PMID33125711
PMCPMC9328389
OpenAlexW3097878033

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.