COVID-19, the clinical syndrome caused by the SARS-CoV-2 virus, has rapidly spread globally causing hundreds of millions of infections and over two million deaths. The potential animal reservoirs for SARS-CoV-2 are currently unknown, however sequence analysis has provided plausible potential candidate species. SARS-CoV-2 binds to the angiotensin I converting enzyme 2 (ACE2) to enable its entry into host cells and establish infection. We analyzed the binding surface of ACE2 from several important animal species to begin to understand the parameters for the ACE2 recognition by the SARS-CoV-2 spike protein receptor binding domain (RBD). We employed Shannon entropy analysis to determine the variability of ACE2 across its sequence and particularly in its RBD interacting region, and assessed differences between various species’ ACE2 and human ACE2. Recombinant ACE2 from human, hamster, horseshoe bat, cat, ferret, and cow were evaluated for RBD binding. A gradient of binding affinities were seen where human and hamster ACE2 were similarly in the low nanomolar range, followed by cat and cow. Surprisingly, horseshoe bat (Rhinolophus sinicus) and ferret (Mustela putorius) ACE2s had poor binding activity compared with the other species’ ACE2. The residue differences and binding properties between the species’ variants provide a framework for understanding ACE2–RBD binding and virus tropism.

中文翻译：

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ACE2 的多样性及其与 SARS-CoV-2 受体结合域的相互作用

COVID-19 是由 SARS-CoV-2 病毒引起的临床综合征，已在全球迅速蔓延，造成数亿人感染和超过 200 万人死亡。SARS-CoV-2 的潜在动物宿主目前尚不清楚，但序列分析提供了合理的潜在候选物种。SARS-CoV-2 与血管紧张素 I 转化酶 2 (ACE2) 结合，使其进入宿主细胞并建立感染。我们分析了来自几个重要动物物种的 ACE2 的结合表面，以开始了解 SARS-CoV-2 刺突蛋白受体结合域 (RBD) 识别 ACE2 的参数。我们采用香农熵分析来确定 ACE2 在其序列中的变异性，特别是在其 RBD 相互作用区域中，并评估了不同物种的 ACE2 和人类 ACE2 之间的差异。评估了来自人类、仓鼠、马蹄蝠、猫、雪貂和牛的重组 ACE2 的 RBD 结合。观察到结合亲和力梯度，其中人和仓鼠 ACE2 在低纳摩尔范围内相似，其次是猫和牛。令人惊讶的是，与其他物种的 ACE2 相比，马蹄蝠 (Rhinolophus sinicus) 和雪貂 (Mustela putorius) ACE2 的结合活性较差。物种变体之间的残基差异和结合特性为理解 ACE2-RBD 结合和病毒嗜性提供了一个框架。与其他物种的 ACE2 相比，马蹄蝠 (Rhinolophus sinicus) 和雪貂 (Mustela putorius) ACE2 的结合活性较差。物种变体之间的残基差异和结合特性为理解 ACE2-RBD 结合和病毒嗜性提供了一个框架。与其他物种的 ACE2 相比，马蹄蝠 (Rhinolophus sinicus) 和雪貂 (Mustela putorius) ACE2 的结合活性较差。物种变体之间的残基差异和结合特性为理解 ACE2-RBD 结合和病毒嗜性提供了一个框架。