ArticleNature communications2021
Distinct mechanisms for TMPRSS2 expression explain organ-specific inhibition of SARS-CoV-2 infection by enzalutamide.
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 66 papers, 1 of them a synthesis that pooled it.
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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
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.
- Safety and Efficacy of Camostat Mesylate for Covid-19: a systematic review and Meta-analysis of Randomized controlled trials.BMC infectious diseases · 2024Pooled it
- 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
- Sexual dimorphism of COVID-19 inspires drug repositioning and host-targeting immunotherapy for viral pneumonia.Signal transduction and targeted therapy · 2026Article
- Ex vivo detection of SARS CoV 2 spike protein in human hair follicles and potential link to telogen effluvium.Scientific reports · 2025Article
- Human Transmembrane Serine Protease 2 (TMPRSS2) on Human Seminal Fluid Extracellular Vesicles Is Proteolytically Active.Journal of extracellular vesicles · 2025Article
- Article
- Novel proteolytic activation of Ebolavirus glycoprotein GP by TMPRSS2 and cathepsin L at an uncharted position can compensate for furin cleavage.Virus research · 2024Article
- MED12 and CDK8/19 Modulate Androgen Receptor Activity and Enzalutamide Response in Prostate Cancer.Endocrinology · 2024Article
- SLC38A9 regulates SARS-CoV-2 viral entry.iScience · 2024Article
- Discovery of a peptide proteolysis-targeting chimera (PROTAC) drug of p300 for prostate cancer therapy.EBioMedicine · 2024Article
- Article
- Ligand-Based Design of Selective Peptidomimetic uPA and TMPRSS2 Inhibitors with Arg Bioisosteres.International journal of molecular sciences · 2024Article
- Genetic association of ACE2 and TMPRSS2 polymorphisms with COVID-19 severity; a single centre study from Egypt.Virology journal · 2024Article
- Article
- Human organoids-on-chips for biomedical research and applications.Theranostics · 2024Review
- Expression of TMPRSS2 is up-regulated by bacterial flagellin, LPS, and Pam3Cys in human airway cells.Life science alliance · 2023Article
- Improving Soluble Expression of SARS-CoV-2 Spike Priming Protease TMPRSS2 with an Artificial Fusing Protein.International journal of molecular sciences · 2023Article
- Sex hormones in SARS-CoV-2 susceptibility: key players or confounders?Nature reviews. Endocrinology · 2023Review
- Lung fibrosis: Post-COVID-19 complications and evidences.International immunopharmacology · 2023Review
- Apalutamide Prevents SARS-CoV-2 Infection in Lung Epithelial Cells and in Human Nasal Epithelial Cells.International journal of molecular sciences · 2023Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
27 authors at 4 institutions in 2 countries.
Funding
Abstract
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly become a global public health threat. The efficacy of several repurposed drugs has been evaluated in clinical trials. Among these drugs, a second-generation antiandrogen agent, enzalutamide, was proposed because it reduces the expression of transmembrane serine protease 2 (TMPRSS2), a key component mediating SARS-CoV-2-driven entry, in prostate cancer cells. However, definitive evidence for the therapeutic efficacy of enzalutamide in COVID-19 is lacking. Here, we evaluated the antiviral efficacy of enzalutamide in prostate cancer cells, lung cancer cells, human lung organoids and Ad-ACE2-transduced mice. Tmprss2 knockout significantly inhibited SARS-CoV-2 infection in vivo. Enzalutamide effectively inhibited SARS-CoV-2 infection in human prostate cells, however, such antiviral efficacy was lacking in human lung cells and organoids. Accordingly, enzalutamide showed no antiviral activity due to the AR-independent TMPRSS2 expression in mouse and human lung epithelial cells. Moreover, we observed distinct AR binding patterns between prostate cells and lung cells and a lack of direct binding of AR to TMPRSS2 regulatory locus in human lung cells. Thus, our findings do not support the postulated protective role of enzalutamide in treating COVID-19 through reducing TMPRSS2 expression in lung cells.
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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.