Angiotensin converting enzyme 2 (ACE2) is the human receptor that interacts with the spike protein of coronaviruses, including the one that produced the 2020 coronavirus pandemic (COVID‐19). Thus, ACE2 is a potential target for drugs that disrupt the interaction of human cells with SARS‐CoV‐2 to abolish infection. There is also interest in drugs that inhibit or activate ACE2, that is, for cardiovascular disorders or colitis. Compounds binding at alternative sites could allosterically affect the interaction with the spike protein. Herein, we review biochemical, chemical biology, and structural information on ACE2, including the recent cryoEM structures of full‐length ACE2. We conclude that ACE2 is very dynamic and that allosteric drugs could be developed to target ACE2. At the time of the 2020 pandemic, we suggest that available ACE2 inhibitors or activators in advanced development should be tested for their ability to allosterically displace the interaction between ACE2 and the spike protein.

中文翻译：

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ACE2，能够感染 SARS-CoV-2 的受体：ACE2 调节剂的生物化学、结构、变构和潜在开发评估。

血管紧张素转换酶 2 (ACE2) 是一种与冠状病毒的刺突蛋白相互作用的人类受体，包括导致 2020 年冠状病毒大流行 (COVID-19) 的刺突蛋白。因此，ACE2 是破坏人类细胞与 SARS-CoV-2 相互作用以消除感染的药物的潜在靶点。人们还对抑制或激活 ACE2（即治疗心血管疾病或结肠炎的药物）感兴趣。在替代位点结合的化合物可能会变构地影响与刺突蛋白的相互作用。在此，我们回顾了 ACE2 的生化、化学生物学和结构信息，包括全长 ACE2 的最新冷冻电镜结构。我们得出的结论是，ACE2 非常活跃，可以开发针对 ACE2 的变构药物。在 2020 年大流行期间，我们建议应对处于高级开发阶段的可用 ACE2 抑制剂或激活剂进行测试，以确定它们以变构方式取代 ACE2 与刺突蛋白之间相互作用的能力。