Evidence map›Paper›PMID 33298900›Full record

ArticleCell discovery2020

Heparan sulfate assists SARS-CoV-2 in cell entry and can be targeted by approved drugs in vitro.

Qi Zhang, Catherine Zhengzheng Chen, Manju Swaroop, Miao Xu, Lihui Wang, Juhyung Lee, Amy Qiu Wang, Manisha Pradhan, Natalie Hagen, Lu Chen and 7 more

Open access · goldAbstract read
In one paragraph

Article in Cell discovery, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers.

0numbers the graph read from it
0cells of the map it votes in
171citing papers in PubMed
4.8field-weighted citation impact, top 3% 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

171 citing papers in PubMed, 241 citations in OpenAlex.

  1. Article
  2. Article
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  4. Article
  5. Article
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  8. Article
  9. Article
  10. Article
  11. Article
  12. Cell entry mechanisms of porcine enteric coronaviruses.The Journal of biological chemistry · 2026
    Review
  13. Host Glycan-Lectin Interplay in SARS-CoV-2 Infection.International journal of molecular sciences · 2026
    Review
  14. Article
  15. Glycosaminoglycans and Their Role in Capillary Walls.Advances in experimental medicine and biology · 2026
    Review
  16. Review
  17. Article
  18. Review
  19. Article
  20. Molecular mechanisms of SARS-CoV-2 entry: implications for biomedical strategies.Microbiology and molecular biology reviews : MMBR · 2025
    Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 1 institution in 1 country.

Qi ZhangLaboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID http://orcid.org/0000-0002-2639-9158
Catherine Zhengzheng ChenNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
Manju SwaroopNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
Miao XuNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
Lihui WangLaboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Juhyung LeeLaboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID http://orcid.org/0000-0002-3638-1496
Amy Qiu WangNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
Manisha PradhanNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
Natalie HagenNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
Lu ChenNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
Min ShenNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
Zhiji LuoNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
Xin XuNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
Yue XuLaboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Wenwei HuangNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
Wei ZhengNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.ORCID http://orcid.org/0000-0003-1034-0757
Yihong YeLaboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA. yihongy@mail.nih.gov.ORCID http://orcid.org/0000-0002-9512-7922
National Institutes of Health · US

Funding

Drug Repurposing Screening for Rare and Neglected DiseasesZIATR000018 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI ZHENG, WEI · 2015 to 2025
$24.6M
6 · The paper itself

Abstract

The cell entry of SARS-CoV-2 has emerged as an attractive drug repurposing target for COVID-19. Here we combine genetics and chemical perturbation to demonstrate that ACE2-mediated entry of SARS-Cov and CoV-2 requires the cell surface heparan sulfate (HS) as an assisting cofactor: ablation of genes involved in HS biosynthesis or incubating cells with a HS mimetic both inhibit Spike-mediated viral entry. We show that heparin/HS binds to Spike directly, and facilitates the attachment of Spike-bearing viral particles to the cell surface to promote viral entry. We screened approved drugs and identified two classes of inhibitors that act via distinct mechanisms to target this entry pathway. Among the drugs characterized, Mitoxantrone is a potent HS inhibitor, while Sunitinib and BNTX disrupt the actin network to indirectly abrogate HS-assisted viral entry. We further show that drugs of the two classes can be combined to generate a synergized activity against SARS-CoV-2-induced cytopathic effect. Altogether, our study establishes HS as an attachment factor that assists SARS coronavirus cell entry and reveals drugs capable of targeting this important step in the viral life cycle.

Identifiers

PMID33298900
PMCPMC7610239
OpenAlexW3094975056

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.