Evidence mapPaperPMID 34210968Full record

ArticleNature communications2021

The antiandrogen enzalutamide downregulates TMPRSS2 and reduces cellular entry of SARS-CoV-2 in human lung cells.

D A Leach, A Mohr, E S Giotis, E Cil, A M Isac, L L Yates, W S Barclay, R M Zwacka, C L Bevan, G N Brooke

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 1 pooled it
7.1field-weighted citation impact, top 2% 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

53 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Impact of Glucose, Inflammation and Phytochemicals onAntioxidants (Basel, Switzerland) · 2025
    Article
  12. Thieno[2,3-Endocrine oncology (Bristol, England) · 2025
    Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Type 1 Diabetes and COVID-19: A Literature Review and Possible Management.International journal of endocrinology and metabolism · 2023
    Review
  20. Proxalutamide reduces SARS-CoV-2 infection and associated inflammatory response.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
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

10 authors at 2 institutions in 1 country.

D A LeachDepartment of Surgery and Cancer, Imperial College London, London, UK.
A MohrSchool of Life Sciences, University of Essex, Colchester, Essex, UK.
E S GiotisSchool of Life Sciences, University of Essex, Colchester, Essex, UK.ORCID 0000-0001-8908-7824
E CilSchool of Life Sciences, University of Essex, Colchester, Essex, UK.ORCID 0000-0002-5097-1548
A M IsacSchool of Life Sciences, University of Essex, Colchester, Essex, UK.
L L YatesNational Heart and Lung Institute, Imperial College London, London, UK.
W S BarclayDepartment of Infectious Diseases, Imperial College London, London, UK.ORCID 0000-0002-3948-0895
R M ZwackaSchool of Life Sciences, University of Essex, Colchester, Essex, UK.
C L Bevan *Department of Surgery and Cancer, Imperial College London, London, UK. charlotte.bevan@imperial.ac.uk.ORCID 0000-0002-7533-0552
G N Brooke *Department of Surgery and Cancer, Imperial College London, London, UK. gbrooke@essex.ac.uk.ORCID 0000-0003-4501-4134
University of Essex · GBImperial College London · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

SARS-CoV-2 attacks various organs, most destructively the lung, and cellular entry requires two host cell surface proteins: ACE2 and TMPRSS2. Downregulation of one or both of these is thus a potential therapeutic approach for COVID-19. TMPRSS2 is a known target of the androgen receptor, a ligand-activated transcription factor; androgen receptor activation increases TMPRSS2 levels in various tissues, most notably prostate. We show here that treatment with the antiandrogen enzalutamide-a well-tolerated drug widely used in advanced prostate cancer-reduces TMPRSS2 levels in human lung cells and in mouse lung. Importantly, antiandrogens significantly reduced SARS-CoV-2 entry and infection in lung cells. In support of this experimental data, analysis of existing datasets shows striking co-expression of AR and TMPRSS2, including in specific lung cell types targeted by SARS-CoV-2. Together, the data presented provides strong evidence to support clinical trials to assess the efficacy of antiandrogens as a treatment option for COVID-19.

Indexed as

COVID-19 Drug TreatmentAndrogen AntagonistsAngiotensin-Converting Enzyme 2AnimalsBenzamidesCOVID-19Down-RegulationFemaleHumansLungMaleMiceNitrilesPhenylthiohydantoinSARS-CoV-2Serine EndopeptidasesACE2 protein, humanAndrogen AntagonistsAngiotensin-Converting Enzyme 2BenzamidesenzalutamideNitrilesPhenylthiohydantoinSerine EndopeptidasesTMPRSS2 protein, human

Identifiers

PMID34210968
PMCPMC8249423
OpenAlexW3174635239

What Socratic 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 Socratic graph.