ArticleiScience2021
Targeting androgen regulation of TMPRSS2 and ACE2 as a therapeutic strategy to combat COVID-19.
Article in iScience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 2 of them syntheses that pooled 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.
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.
Who cites it
65 citing papers in PubMed, 2 syntheses or guidelines pooled it, 103 citations in OpenAlex.
- Protective trend of anti-androgen therapy during the COVID-19 pandemic: A meta-analysis.The Journal of infection · 2022Pooled it
- Genetic susceptibility of COVID-19: a systematic review of current evidence.European journal of medical research · 2021Pooled it
- Effect of Androgen Suppression on Clinical Outcomes in Hospitalized Men With COVID-19: The HITCH Randomized Clinical Trial.JAMA network open · 2022Trial
- TMPRSS2 inhibitors with broad-spectrum efficacy against SARS-CoV-2 (JN.1) and influenza A (H1N1) viruses protect mice from influenza A infection.Emerging microbes & infections · 2026Article
- Sexual dimorphism of COVID-19 inspires drug repositioning and host-targeting immunotherapy for viral pneumonia.Signal transduction and targeted therapy · 2026Article
- Mapping cellular signaling pathways involved in SARS-CoV-2 spike protein-mediated syncytia formation.Infectious diseases & immunity · 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
- TMPRSS2: A Key Host Factor in SARS-CoV-2 Infection and Potential Therapeutic Target.Medeniyet medical journal · 2025Article
- CRISPR-Cas9 genetic screens reveal regulation of TMPRSS2 by the Elongin BC-VHL complex.Scientific reports · 2025Article
- Bridging Cancer and COVID-19: The Complex Interplay of ACE2 and TMPRSS2.Cancer medicine · 2025Review
- Anti-inflammatory effects ofFrontiers in pharmacology · 2025Article
- Zinc as a Possible Critical Element to Prevent Harmful Effects of COVID-19 on Testicular Function: a Narrative Review.Reproductive sciences (Thousand Oaks, Calif.) · 2024Review
- Aromatase, testosterone, TMPRSS2: determinants of COVID-19 severity.Biology of sex differences · 2024Article
- Article
- Potential Effects of Hyperglycemia on SARS-CoV-2 Entry Mechanisms in Pancreatic Beta Cells.Viruses · 2024Review
- Sex hormones in COVID-19 severity: The quest for evidence and influence mechanisms.Journal of cellular and molecular medicine · 2024Review
- Anti-COVID-19 Potential of Withaferin-A and Caffeic Acid Phenethyl Ester.Current topics in medicinal chemistry · 2024Article
- Inhalation of ACE2 as a therapeutic target on sex-bias differences in SARS-CoV-2 infection and variant of concern.iScience · 2023Article
- Proxalutamide reduces SARS-CoV-2 infection and associated inflammatory response.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Renin-Angiotensin System and Sex Differences in COVID-19: A Critical Assessment.Circulation research · 2023Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Epidemiological data showing increased severity and mortality of COVID-19 in men suggests a potential role for androgen in SARS-CoV-2 infection. Here, we present evidence for the transcriptional regulation of SARS-CoV-2 host cell receptor ACE2 and TMPRSS2 by androgen in mouse and human cells. Additionally, we demonstrate the endogenous interaction between TMPRSS2 and ACE2 in human cells and validate ACE2 as a TMPRSS2 substrate. Furthermore, camostat-a TMPRSS2 inhibitor-blocked the cleavage of pseudotype SARS-CoV-2 surface Spike without disrupting TMPRSS2-ACE2 interaction, thus providing evidence for the first time of a direct role of TMPRSS2 in priming the SARS-CoV-2 Spike, required for viral fusion to the host cell. Importantly, androgen-deprivation, anti-androgens, or camostat attenuated the SARS-CoV-2 S-mediated cellular entry. Together, our data provide a strong rationale for clinical evaluations of TMPRSS2 inhibitors and androgen-deprivation therapy/androgen receptor antagonists alone or in combination with antiviral drugs as early as clinically possible to prevent COVID-19 progression.
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Identifiers
What OpenQuestion holds
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 OpenQuestion graph.