Structural basis of receptor recognition by SARS-CoV-2

Jian Shang, Gang Ye, Ke Shi, Yushun Wan, Chuming Luo, Hideki Aihara, Qibin Geng, Ashley Auerbach, Fang Li

Research output: Contribution to journalArticlepeer-review

2368 Scopus citations


A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) recently emerged and is rapidly spreading in humans, causing COVID-191,2. 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 humans3,4. 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.

Original languageEnglish (US)
Pages (from-to)221-224
Number of pages4
Issue number7807
StatePublished - May 14 2020

Bibliographical note

Funding Information:
Acknowledgements This work was supported by NIH grants R01AI089728 and R01AI110700 (to F.L.) and R35GM118047 (to H.A.) and is based on research conducted at the Northeastern Collaborative Access Team beamlines, which are supported by NIH grants P30GM124165 and S10OD021527, and DOE contract DE-AC02-06CH11357. We thank staff at Advanced Photon Source beamline 24-ID-E for assistance in data collection and Y. V. Jiang for statistical consultation and edits to the manuscript.

Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.


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