Spironolactone may provide protection from SARS-CoV-2: Targeting androgens, angiotensin converting enzyme 2 (ACE2), and renin-angiotensin-aldosterone system (RAAS)
Spironolactone may provide protection from SARS-CoV-2: Targeting androgens, angiotensin converting enzyme 2 (ACE2), and renin-angiotensin-aldosterone system (RAAS)
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DOI：
10.1016/j.mehy.2020.110112
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发表时间：
2020-10-01
影响因子：
4.7
通讯作者：
Wambier, Carlos G.
中科院分区：
文献类型：
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作者：
Cadegiani, Flavio A.;Goren, Andy;Wambier, Carlos G.
在冠状病毒病 19 (COVID-19) 中，四个主要因素与较差的预后相关：衰老、高血压、肥胖和雄激素暴露。血管紧张素转换酶 2 (ACE2) 受体、肾素-血管紧张素-醛固酮系统 (RAAS) 的调节以及跨膜丝氨酸蛋白酶 2 (TMPRSS2) 的作用对于严重急性呼吸综合征冠状病毒-2 (SARS-CoV-2) 细胞的进入和感染至关重要。 ACE2 表达和 RAAS 在高血压和肥胖症中异常，而 TMPRSS2 在暴露于雄激素时过度表达，这可能解释了为什么这些因素在 COVID19 中过度表达。在 SARS-CoV-2 的治疗靶点中，我们假设螺内酯是一种长期使用且安全的盐皮质激素和雄激素受体拮抗剂，具有有效的抗高血压、心脏保护、肾保护和抗雄激素特性。在不同地点提供多效性行动来预防 COVID-19。目前的数据表明，螺内酯可以同时减轻异常的 ACE2 表达，纠正膜附着和游离循环 ACE2 以及血管紧张素 II 和血管紧张素 (1-7) (Ang-(1-7)) 之间的平衡，抑制雄激素介导的 TMPRSS2 活性，并抑制肥胖相关的 RAAS 功能障碍，从而减少病毒启动。因此，螺内酯可以提供针对 SARS-CoV2 的保护，并且具有足够的合理性进行临床测试，特别是在 COVID-19 的早期阶段。
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 COVID19.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-CoV2, and has sufficient plausibility to be clinically tested, particularly in the early stages of COVID-19.