ArticleMedical hypotheses2020
Spironolactone may provide protection from SARS-CoV-2: Targeting androgens, angiotensin converting enzyme 2 (ACE2), and renin-angiotensin-aldosterone system (RAAS).
Article in Medical hypotheses, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Cardiovascular Disease and COVID-19: Insight From Cases With Heart Failure.Frontiers in cardiovascular medicine · 2021Pooled it
- The Effect of Potassium Canrenoate (Mineralocorticoid Receptor Antagonist) on the Markers of Inflammation in the Treatment of COVID-19 Pneumonia and Fibrosis-A Secondary Analysis of Randomized Placebo-Controlled Clinical Trial.International journal of molecular sciences · 2023Trial
- No influence of spironolactone on plasma concentrations of angiotensin-converting enzyme 2: Findings from the HOMAGE randomized trial.Archives of cardiovascular diseases · 2021Trial
- Comparative Effects of Mineralocorticoid Receptor Antagonism on Organ Dysfunction in COVID-19-Associated ARDS.Biomedicines · 2026Article
- Use of chronic medications and risk of death due to COVID-19 in hospitalised patients.European journal of hospital pharmacy : science and practice · 2024Article
- Sex-Specific Total Testosterone and Dehydroepiandrosterone Sulfate Status in Noncritically Ill Hospitalized Patients with Coronavirus Disease 2019: A Cross-Sectional Study.International journal of fertility & sterility · 2023Article
- DrugRep-HeSiaGraph: when heterogenous siamese neural network meets knowledge graphs for drug repurposing.BMC bioinformatics · 2023Article
- COVID-19 therapeutics: Clinical application of repurposed drugs and futuristic strategies for target-based drug discovery.Genes & diseases · 2023Review
- Exploration of multifaceted molecular mechanism of angiotensin-converting enzyme 2 (ACE2) in pathogenesis of various diseases.Heliyon · 2023Review
- Angiotensin-Converting Enzyme 2 Expression and Severity of SARS-CoV-2 Infection.Microorganisms · 2023Review
- Counter-regulatory renin-angiotensin system in hypertension: Review and update in the era of COVID-19 pandemic.Biochemical pharmacology · 2023Review
- Crosstalk between estrogen, dendritic cells, and SARS-CoV-2 infection.Reviews in medical virology · 2022Review
- Races of small molecule clinical trials for the treatment of COVID-19: An up-to-date comprehensive review.Drug development research · 2022Review
- The Biological Causes and Consequences of COVID-19: ACE I/D Polymorphism and In-Silico Screening of Potential Bioactive Phytochemicals Against COVID-19.Bioinformatics and biology insights · 2022Article
- The Effects of Different Classes of Antihypertensive Drugs on Patients with COVID-19 and Hypertension: A Mini-Review.International journal of hypertension · 2022Review
- Androgens in SARS-CoV-2 coronavirus infections.Physiological research · 2021Review
- Article
- Repurposing Cardio-Metabolic Drugs to Fight Covid19.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2021Article
- Early COVID-19 therapy with azithromycin plus nitazoxanide, ivermectin or hydroxychloroquine in outpatient settings significantly improved COVID-19 outcomes compared to known outcomes in untreated patients.New microbes and new infections · 2021Article
- An overview of sex hormones in relation to SARS-CoV-2 infection.Future virology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In coronavirus disease-19 (COVID-19), four major factors have been correlated with worse prognosis: aging, hypertension, obesity, and exposure to androgen hormones. Angiotensin-converting enzyme-2 (ACE2) receptor, regulation of the renin-angiotensin-aldosterone system (RAAS), and transmembrane serine protease 2 (TMPRSS2) action are critical for the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) cell entry and infectivity. ACE2 expression and RAAS are abnormal in hypertension and obesity, while TMPRSS2 is overexpressed when exposed to androgens, which may justify why these factors are overrepresented in COVID-19. Among therapeutic targets for SARS-CoV-2, we hypothesized that spironolactone, a long used and safe mineralocorticoid and androgen receptors antagonist, with effective anti-hypertensive, cardioprotective, nephroprotective, and anti-androgenic properties may offer pleiotropic actions in different sites to protect from COVID-19. Current data shows that spironolactone may concurrently mitigate abnormal ACE2 expression, correct the balances membrane-attached and free circulating ACE2 and between angiotensin II and Angiotensin-(1-7) (Ang-(1-7)), suppress androgen-mediated TMPRSS2 activity, and inhibit obesity-related RAAS dysfunctions, with consequent decrease of viral priming. Hence, spironolactone may provide protection from SARS-CoV-2, and has sufficient plausibility to be clinically tested, particularly in the early stages of 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 OpenQuestion graph.