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.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Angiotensin-Converting Enzyme 2
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Animals
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Betacoronavirus / chemistry*
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Betacoronavirus / drug effects
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Betacoronavirus / metabolism
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Binding Sites
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COVID-19
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China / epidemiology
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Chiroptera / virology
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Coronavirus / chemistry
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Coronavirus / isolation & purification
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Coronavirus Infections / drug therapy
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Coronavirus Infections / epidemiology
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Coronavirus Infections / transmission
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Coronavirus Infections / virology
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Crystallization
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Crystallography, X-Ray
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Disease Reservoirs / virology
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Eutheria / virology
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Humans
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Models, Molecular
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Pandemics
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Peptidyl-Dipeptidase A / chemistry*
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Peptidyl-Dipeptidase A / metabolism*
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Pneumonia, Viral / drug therapy
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Pneumonia, Viral / epidemiology
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Pneumonia, Viral / transmission
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Pneumonia, Viral / virology
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Protein Binding
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Protein Domains
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Protein Stability
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Receptors, Virus / chemistry*
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Receptors, Virus / metabolism*
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SARS-CoV-2
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Severe acute respiratory syndrome-related coronavirus / chemistry
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Spike Glycoprotein, Coronavirus / chemistry*
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Spike Glycoprotein, Coronavirus / genetics
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Spike Glycoprotein, Coronavirus / metabolism*
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Zoonoses / epidemiology
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Zoonoses / transmission
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Zoonoses / virology*
Substances
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Receptors, Virus
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Spike Glycoprotein, Coronavirus
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spike protein, SARS-CoV-2
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Peptidyl-Dipeptidase A
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ACE2 protein, human
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Angiotensin-Converting Enzyme 2