Tags

Type your tag names separated by a space and hit enter

Spironolactone may provide protection from SARS-CoV-2: Targeting androgens, angiotensin converting enzyme 2 (ACE2), and renin-angiotensin-aldosterone system (RAAS).
Med Hypotheses. 2020 Oct; 143:110112.MH

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.

Authors+Show Affiliations

Department of Endocrinology, Federal University of São Paulo, SP, Brazil. Electronic address: flavio.cadegiani@unifesp.br.Warren Alpert Medical School of Brown University, Providence, RI, USA.Warren Alpert Medical School of Brown University, Providence, RI, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32721806

Citation

Cadegiani, Flavio A., et al. "Spironolactone May Provide Protection From SARS-CoV-2: Targeting Androgens, Angiotensin Converting Enzyme 2 (ACE2), and Renin-angiotensin-aldosterone System (RAAS)." Medical Hypotheses, vol. 143, 2020, p. 110112.
Cadegiani FA, Goren A, Wambier CG. Spironolactone may provide protection from SARS-CoV-2: Targeting androgens, angiotensin converting enzyme 2 (ACE2), and renin-angiotensin-aldosterone system (RAAS). Med Hypotheses. 2020;143:110112.
Cadegiani, F. A., Goren, A., & Wambier, C. G. (2020). Spironolactone may provide protection from SARS-CoV-2: Targeting androgens, angiotensin converting enzyme 2 (ACE2), and renin-angiotensin-aldosterone system (RAAS). Medical Hypotheses, 143, 110112. https://doi.org/10.1016/j.mehy.2020.110112
Cadegiani FA, Goren A, Wambier CG. Spironolactone May Provide Protection From SARS-CoV-2: Targeting Androgens, Angiotensin Converting Enzyme 2 (ACE2), and Renin-angiotensin-aldosterone System (RAAS). Med Hypotheses. 2020;143:110112. PubMed PMID: 32721806.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spironolactone may provide protection from SARS-CoV-2: Targeting androgens, angiotensin converting enzyme 2 (ACE2), and renin-angiotensin-aldosterone system (RAAS). AU - Cadegiani,Flavio A, AU - Goren,Andy, AU - Wambier,Carlos G, Y1 - 2020/07/16/ PY - 2020/07/09/received PY - 2020/07/13/accepted PY - 2020/7/30/pubmed PY - 2020/7/30/medline PY - 2020/7/30/entrez KW - ACE2 KW - COVID-19 KW - Pandemic KW - SARS-CoV-2 KW - Spironolactone KW - TMPRS22 SP - 110112 EP - 110112 JF - Medical hypotheses JO - Med Hypotheses VL - 143 N2 - 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. SN - 1532-2777 UR - https://www.unboundmedicine.com/medline/citation/32721806/Spironolactone_may_provide_protection_from_SARS_CoV_2:_Targeting_androgens_angiotensin_converting_enzyme_2__ACE2__and_renin_angiotensin_aldosterone_system__RAAS__ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-9877(20)32142-3 DB - PRIME DP - Unbound Medicine ER -