The COVID ‐19 pandemic caused by SARS ‐CoV‐2 has is a global health challenge. Angiotensin‐converting enzyme 2 (ACE 2 ) is the host receptor for SARS ‐CoV‐2 entry. Recent studies have suggested that patients with hypertension and diabetes treated with ACE inhibitors (ACEI s) or angiotensin receptor blockers have a higher risk of COVID ‐19 infection as these drugs could upregulate ACE 2 , motivating the study of ACE 2 modulation by drugs in current clinical use. Here, we mined published datasets to determine the effects of hundreds of clinically approved drugs on ACE 2 expression. We find that ACEI s are enriched for ACE 2‐upregulating drugs, while antineoplastic agents are enriched for ACE 2‐downregulating drugs. Vorinostat and isotretinoin are the top ACE 2 up/downregulators, respectively, in cell lines. Dexamethasone, a corticosteroid used in treating severe acute respiratory syndrome and COVID ‐19, significantly upregulates ACE 2 both in vitro and in vivo . Further top ACE 2 regulators in vivo or in primary cells include erlotinib and bleomycin in the lung and vancomycin, cisplatin, and probenecid in the kidney. Our study provides leads for future work studying ACE 2 expression modulators.

中文翻译：

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临床批准的修饰 ACE2 表达药物的体外和体内鉴定。

由 SARS ‐CoV-2 引起的 COVID ‐19 大流行是一项全球健康挑战。血管紧张素转换酶 2 ( ACE 2 ) 是 SARS ‐CoV-2 进入的宿主受体。最近的研究表明，使用 ACE 抑制剂 (ACEI) 或血管紧张素受体阻滞剂治疗的高血压和糖尿病患者感染 COVID-19 的风险较高，因为这些药物可能上调 ACE 2 ，推动了当前药物调节 ACE 2的研究。临床使用。在这里，我们挖掘了已发表的数据集，以确定数百种临床批准的药物对ACE 2表达的影响。我们发现，ACEI 富含ACE 2上调药物，而抗肿瘤药物则富含ACE 2下调药物。伏立诺他和异维A酸分别是细胞系中最主要的ACE 2上调/下调调节剂。地塞米松是一种用于治疗严重急性呼吸综合征和 COVID-19 的皮质类固醇，在体外和体内均显着上调ACE 2。体内或原代细胞中的其他顶级ACE 2调节剂包括肺中的厄洛替尼和博莱霉素以及肾中的万古霉素、顺铂和丙磺舒。我们的研究为未来研究ACE 2表达调节剂的工作提供了线索。