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Structural basis of receptor recognition by SARS-CoV-2.
Nature. 2020 05; 581(7807):221-224.Nat

Abstract

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.

Authors+Show Affiliations

Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN, USA.Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN, USA.Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN, USA.Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN, USA.Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN, USA.Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN, USA.Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN, USA. lifang@umn.edu.

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

32225175

Citation

Shang, Jian, et al. "Structural Basis of Receptor Recognition By SARS-CoV-2." Nature, vol. 581, no. 7807, 2020, pp. 221-224.
Shang J, Ye G, Shi K, et al. Structural basis of receptor recognition by SARS-CoV-2. Nature. 2020;581(7807):221-224.
Shang, J., Ye, G., Shi, K., Wan, Y., Luo, C., Aihara, H., Geng, Q., Auerbach, A., & Li, F. (2020). Structural basis of receptor recognition by SARS-CoV-2. Nature, 581(7807), 221-224. https://doi.org/10.1038/s41586-020-2179-y
Shang J, et al. Structural Basis of Receptor Recognition By SARS-CoV-2. Nature. 2020;581(7807):221-224. PubMed PMID: 32225175.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structural basis of receptor recognition by SARS-CoV-2. AU - Shang,Jian, AU - Ye,Gang, AU - Shi,Ke, AU - Wan,Yushun, AU - Luo,Chuming, AU - Aihara,Hideki, AU - Geng,Qibin, AU - Auerbach,Ashley, AU - Li,Fang, Y1 - 2020/03/30/ PY - 2020/02/16/received PY - 2020/03/20/accepted PY - 2020/4/1/pubmed PY - 2020/5/20/medline PY - 2020/4/1/entrez SP - 221 EP - 224 JF - Nature JO - Nature VL - 581 IS - 7807 N2 - 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. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/32225175/Structural_basis_of_receptor_recognition_by_SARS_CoV_2_ L2 - https://doi.org/10.1038/s41586-020-2179-y DB - PRIME DP - Unbound Medicine ER -