Angiotensin-converting enzyme 2 (ACE2) is a metallopeptidase that primarily functions as a negative regulator of renin angiotensin system (RAS) by converting angiotensin II (Ang II) to angiotensin 1-7. Contrary to this, another RAS component, angiotensin-converting enzyme (ACE) catalyzes synthesis of Ang II from angiotensin I (Ang I) that functions as active compound in blood pressure regulation. This indicates importance of ACE/ACE2 level in regulating blood pressure by targeting Ang II. An outbreak of severe acute respiratory syndrome (SARS) highlighted the additional role of ACE2 as a receptor for SARS coronavirus (SARS-CoV) infection. ACE2 is a functional receptor for SARS-CoV and SARS-CoV-2. Activation of spike (S)-protein by either type II transmembrane serine proteases (TTSPs) or cathepsin-mediated cleavage initiates receptor binding and viral entry. In addition to TTSPs, ACE2 can also be trimmed by ADAM 17 (a disintegrin and metalloproteinase 17) that competes for the same receptor. Cleavage by TTSPs activates ACE2 receptor for binding, whereas ADAM17 releases extracellular fragment called soluble ACE2 (sACE2). Structural studies of both ACE2 and S-protein have found critical sites involved in binding mechanism. In addition to studies on structural motifs, few single-nucleotide polymorphism (SNPs) studies have been done to find an association between genetic variants and SARS susceptibility. Though no association was found in those reports, but seeing the non-reproducibility of SNP studies among different ethnic groups, screening of ACE2 SNPs in individual population can be undertaken. Thus, screening for novel SNPs focussing on recently identified critical regions of ACE2 can be targeted to monitor susceptibility towards coronavirus disease 2019 (COVID-19).

中文翻译：

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COVID-19 易感性：ACE2 多态性的潜力


血管紧张素转换酶 2 (ACE2) 是一种金属肽酶，主要通过将血管紧张素 II (Ang II) 转化为血管紧张素 1-7 来充当肾素血管紧张素系统 (RAS) 的负调节因子。与此相反，另一种 RAS 成分血管紧张素转化酶 (ACE) 催化血管紧张素 I (Ang I) 合成 Ang II，而血管紧张素 I (Ang I) 是血压调节中的活性化合物。这表明 ACE/ACE2 水平在通过靶向 Ang II 调节血压中的重要性。严重急性呼吸综合征 (SARS) 的爆发凸显了 ACE2 作为 SARS 冠状病毒 (SARS-CoV) 感染受体的额外作用。 ACE2 是 SARS-CoV 和 SARS-CoV-2 的功能性受体。 II 型跨膜丝氨酸蛋白酶 (TTSP) 或组织蛋白酶介导的切割激活刺突 (S) 蛋白，从而启动受体结合和病毒进入。除了 TTSP 之外，ACE2 还可以被竞争同一受体的 ADAM 17（一种解整合素和金属蛋白酶 17）修剪。 TTSP 的裂解会激活 ACE2 受体进行结合，而 ADAM17 会释放称为可溶性 ACE2 (sACE2) 的细胞外片段。 ACE2 和 S 蛋白的结构研究发现了参与结合机制的关键位点。除了结构基序的研究之外，很少有单核苷酸多态性 (SNP) 研究来寻找遗传变异与 SARS 易感性之间的关联。虽然这些报告没有发现关联，但鉴于不同种族间SNP研究的不可重复性，可以在个体人群中进行ACE2 SNP筛查。因此，针对最近发现的 ACE2 关键区域的新型 SNP 筛选可以有针对性地监测 2019 年冠状病毒病 (COVID-19) 的易感性。