A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) recently emerged and is rapidly spreading in humans, causing COVID-19^1,2. A key to tackling this pandemic is to understand the receptor recognition mechanism of the virus, which regulates its infectivity, pathogenesis and host range. SARS-CoV-2 and SARS-CoV recognize the same receptor—angiotensin-converting enzyme 2 (ACE2)—in humans^3,4. Here we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 (engineered to facilitate crystallization) in complex with ACE2. In comparison with the SARS-CoV RBD, an ACE2-binding ridge in SARS-CoV-2 RBD has a more compact conformation; moreover, several residue changes in the SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD–ACE2 interface. These structural features of SARS-CoV-2 RBD increase its ACE2-binding affinity. Additionally, we show that RaTG13, a bat coronavirus that is closely related to SARS-CoV-2, also uses human ACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV and RaTG13 in ACE2 recognition shed light on the potential animal-to-human transmission of SARS-CoV-2. This study provides guidance for intervention strategies that target receptor recognition by SARS-CoV-2.

最近出现了一种新型严重急性呼吸综合征 (SARS) 样冠状病毒 (SARS-CoV-2)，并在人类中迅速传播，导致了 COVID-19 ^1,2 。应对这一流行病的关键是了解病毒的受体识别机制，该机制调节其感染性、发病机制和宿主范围。 SARS-CoV-2 和 SARS-CoV 在人类中识别相同的受体——血管紧张素转换酶 2 (ACE2) ^3,4 。在这里，我们确定了 SARS-CoV-2 刺突蛋白（经过改造以促进结晶）与 ACE2 复合物的受体结合域 (RBD) 的晶体结构。与SARS-CoV RBD相比，SARS-CoV-2 RBD中的ACE2结合脊具有更紧凑的构象；此外，SARS-CoV-2 RBD 中的几个残基变化稳定了 RBD-ACE2 界面上的两个病毒结合热点。 SARS-CoV-2 RBD 的这些结构特征增加了其 ACE2 结合亲和力。此外，我们还发现 RaTG13（一种与 SARS-CoV-2 密切相关的蝙蝠冠状病毒）也使用人类 ACE2 作为其受体。 SARS-COV-2、SARS-COV 和 RaTG13 在 ACE2 识别方面的差异揭示了 SARS-COV-2 在动物到人类之间传播的潜在可能性。这项研究为针对 SARS-CoV-2 受体识别的干预策略提供了指导。