From the Division of Nephrology and Hypertension, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
Hypertension. 2020 Nov;76(5):1339-1349. doi: 10.1161/HYPERTENSIONAHA.120.15256. Epub 2020 Aug 27.
Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 originated from Wuhan, China, in December 2019 and rapidly spread to other areas worldwide. Since then, coronavirus disease 2019 (COVID-19) has reached pandemic proportions with >570 000 deaths globally by mid-July 2020. The magnitude of the outbreak and the potentially severe clinical course of COVID-19 has led to a burst of scientific research on this novel coronavirus and its host receptor ACE (angiotensin-converting enzyme)-2. ACE2 is a homolog of the ACE that acts on several substrates in the renin-Ang (angiotensin) system. With unprecedented speed, scientific research has solved the structure of SARS-CoV-2 and imaged its binding with the ACE2 receptor. In SARS-CoV-2 infection, the viral S (spike) protein receptor-binding domain binds to ACE2 to enter the host cell. ACE2 expression in the lungs is relatively low, but it is present in type II pneumocytes-a cell type also endowed with TMPRSS2 (transmembrane protease serine 2). This protease is critical for priming the SARS-CoV-2 S protein to complex with ACE2 and enter the cells. Herein, we review the current understanding of the interaction of SARS-CoV-2 with ACE2 as it has rapidly unfolded over the last months. While it should not be assumed that we have a complete picture of SARS-CoV-2 mechanism of infection and its interaction with ACE2, much has been learned with clear therapeutic implications. Potential therapies aimed at intercepting SARS-CoV-2 from reaching the full-length membrane-bound ACE2 receptor using soluble ACE2 protein and other potential approaches are briefly discussed as well.
严重急性呼吸综合征冠状病毒（SARS-CoV-2）源自 2019 年 12 月中国武汉，迅速传播到世界其他地区。自那时以来，冠状病毒病 2019（COVID-19）已达到大流行程度，截至 2020 年 7 月中旬，全球死亡人数超过 57 万。疫情的规模以及 COVID-19 潜在的严重临床病程导致了针对这种新型冠状病毒及其宿主受体 ACE（血管紧张素转换酶）-2 的大量科学研究。ACE2 是 ACE 的同源物，作用于肾素-血管紧张素（angiotensin）系统中的几种底物。随着科学研究的快速发展，已经解决了 SARS-CoV-2 的结构，并对其与 ACE2 受体的结合进行了成像。在 SARS-CoV-2 感染中，病毒 S（刺突）蛋白受体结合域与 ACE2 结合以进入宿主细胞。肺中的 ACE2 表达相对较低，但存在于 II 型肺泡细胞中-一种也具有 TMPRSS2（跨膜蛋白酶丝氨酸 2）的细胞类型。这种蛋白酶对于 SARS-CoV-2 S 蛋白与 ACE2 结合并进入细胞的初步激活至关重要。在此，我们回顾了过去几个月中 SARS-CoV-2 与 ACE2 相互作用的最新认识。虽然我们不应假设我们对 SARS-CoV-2 感染机制及其与 ACE2 的相互作用有完整的了解，但已经学到了很多具有明确治疗意义的知识。还简要讨论了旨在使用可溶性 ACE2 蛋白和其他潜在方法阻止 SARS-CoV-2 到达全长膜结合 ACE2 受体的潜在治疗方法。
