Do Anti-androgens Have Potential as Therapeutics for COVID-19?
Do Anti-androgens Have Potential as Therapeutics for COVID-19?
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DOI：
10.1210/endocr/bqab114
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发表时间：
2021-08-01
期刊：
影响因子：
4.8
通讯作者：
Mauvais-Jarvis F
中科院分区：
文献类型：
--
作者：
Mauvais-Jarvis F
2019 年冠状病毒病 (COVID-19) 的特点是严重程度存在性别差异，男性的住院率和死亡率高于女性。严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 是导致 COVID-19 的病毒，病毒刺突糖蛋白识别并附着在血管紧张素转换酶 2 跨膜蛋白上，随后刺突蛋白被细胞表面跨膜蛋白酶丝氨酸 2 (TMPRSS2) 裂解和激活，从而感染细胞。在前列腺癌细胞中，作用于雄激素受体的雄激素会增加 TMPRSS2 的表达，这导致了这样的假设：肺部 TMPRSS2 的雄激素依赖性表达可能会增加男性对严重 COVID-19 的易感性，因此，抑制雄激素的产生或作用可能会通过减少 SARS-CoV-2 扩增来减轻 COVID-19 的严重程度。几项正在进行的临床试验正在测试雄激素剥夺疗法或抗雄激素药物缓解 COVID-19 的能力。 本视角讨论了雄激素受体 (AR) 对细胞表面跨膜蛋白酶丝氨酸 2 (TMPRSS2) 表达和严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染作用的快速发展领域的临床和分子进展，以及抗雄激素对男性患者 2019 年冠状病毒病 (COVID-19) 严重程度的潜在影响。它讨论了当前研究的局限性并为未来的方向提供了见解。
Coronavirus disease 2019 (COVID-19) is characterized by a gender disparity in severity, with men exhibiting higher hospitalization and mortality rates than women. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, infects cells following recognition and attachment of the viral spike glycoprotein to the angiotensin-converting enzyme 2 transmembrane protein, followed by spike protein cleavage and activation by cell surface transmembrane protease serine 2 (TMPRSS2). In prostate cancer cells, androgen acting on the androgen receptor increases TMPRSS2 expression, which has led to the hypothesis that androgen-dependent expression of TMPRSS2 in the lung may increase men’s susceptibility to severe COVID-19 and that, accordingly, suppressing androgen production or action may mitigate COVID-19 severity by reducing SARS-CoV-2 amplification. Several ongoing clinical trials are testing the ability of androgen deprivation therapies or anti-androgens to mitigate COVID-19. This perspective discusses clinical and molecular advances on the rapidly evolving field of androgen receptor (AR) action on cell surface transmembrane protease serine 2 (TMPRSS2) expression and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the potential effect of anti-androgens on coronavirus disease 2019 (COVID-19) severity in male patients. It discusses limitations of current studies and offers insight for future directions.
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