ArticleNature communications2021
The antiandrogen enzalutamide downregulates TMPRSS2 and reduces cellular entry of SARS-CoV-2 in human lung cells.
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.
What it found
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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.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Protective trend of anti-androgen therapy during the COVID-19 pandemic: A meta-analysis.The Journal of infection · 2022Pooled it
- Phase 2 randomised placebo-controlled trial of spironolactone and dexamethasone versus dexamethasone in COVID-19 hospitalised patients in Delhi.BMC infectious diseases · 2023Trial
- A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome: No Evidence of Benefit, Supported by Epidemiology and In Vitro Data.European urology · 2022Trial
- Lock out: targeting TMPRSS2 to block influenza and coronaviruses.Journal of virology · 2026Review
- Symptom Trajectories and Long-Term Sequelae of COVID-19: A Matched Case-Control Study with Population-Based Controls.Journal of clinical medicine · 2026Article
- Sexual dimorphism of COVID-19 inspires drug repositioning and host-targeting immunotherapy for viral pneumonia.Signal transduction and targeted therapy · 2026Article
- Sex and the Multidimensional Prognostic Index in 3.5-year post-COVID-19 mortality among older adults: evidence of a time-varying effect.Internal and emergency medicine · 2026Article
- Disruption of androgen receptor-cofactor interactions by the RNA-binding protein FUS/TLS alters androgen signalling in prostate cancer.Oncogene · 2026Article
- TMPRSS2 Expression in Lung Tissue of Prostatic Adenocarcinoma Patients: Androgen Deprivation Therapy and Relevance to SARS-CoV-2 Infection.Current issues in molecular biology · 2025Article
- ACE-2 blockade and TMPRSS2 inhibition mitigate SARS-CoV-2 severity following cigarette smoke exposure in airway epithelial cellsMolecular therapy. Nucleic acids · 2025Article
- Impact of Glucose, Inflammation and Phytochemicals onAntioxidants (Basel, Switzerland) · 2025Article
- Thieno[2,3-Endocrine oncology (Bristol, England) · 2025Article
- Article
- Review
- SARS-CoV-2 N protein-induced Dicer, XPO5, SRSF3, and hnRNPA3 downregulation causes pneumonia.Nature communications · 2024Article
- Sex hormones in COVID-19 severity: The quest for evidence and influence mechanisms.Journal of cellular and molecular medicine · 2024Review
- Nucleosome reorganisation in breast cancer tissues.Clinical epigenetics · 2024Article
- Review
- Type 1 Diabetes and COVID-19: A Literature Review and Possible Management.International journal of endocrinology and metabolism · 2023Review
- Proxalutamide reduces SARS-CoV-2 infection and associated inflammatory response.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
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.