Structural basis of receptor recognition by SARS-CoV-2

By J. Shang, G. Ye, K. Shi, Yushun Wan, C. Luo, H. Aihara, Q. Geng, Ashley A. Auerbach, Fang Li. 2020

3,460 citations recorded by the source corpus.

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. The crystal structure of the receptor-binding domain of the SARS-CoV-2 spike in complex with human ACE2, compared with the receptor-binding domain of SARS-CoV, sheds light on the structural features that increase its binding affinity to ACE2.

Subfields: Infectious Diseases

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Infectious Diseases

1. D. Veesler
2. A. Walls
3. M. A. Tortorici
4. Fang Li
5. F. Krammer
6. F. Amanat
7. J. Shang
8. Yushun Wan

Citations in the corpus

• Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 (2020, neutral): “Structures of the SARS-CoV-2 S receptor-binding domain (RBD) in complex with ACE2 defined key residues involved in recognition and guide surveillance studies aiming to detect the emergence of mutants with altered binding affinity for ACE2 or distinct antigenicity (Lan et al., 2020; Shang et al., 202”
• A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS (2020, neutral): “In view of the ongoing COVID-19 pandemic and frequent MERS outbreaks, we sought to further develop vaccines against these two CoVs for pilot scale production in GMP grade manufacturing.”
• A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection (2020, background): “converting enzyme 2 (hACE2), and subsequently by fusion between the viral envelope and the host cell lipid bilayer mediated by the S2 subunit (13, 14).”
• Cell entry mechanisms of SARS-CoV-2 (2020, methodology): “This result is different from our recent report that SARS-CoV-2 RBD binds to hACE2 with significantly higher affinity than SARS-CoV RBD does, which was detected using surface plasmon resonance (SPR) (30).”
• Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach (2020, neutral): “In spite of The SARS-CoV-2 genome share about 82% sequence identity with SARS-CoV and MERS-CoV and > 90% sequence identity for essential enzymes and structural proteins , those variations on the RBD domain of Spike protein change completely the mechanism of the pathology, making each of the coronavi”
• Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding (2020, neutral): “Within the newly described SARS-CoV-2 clade, GD-Pangolin binds ACE2 with slightly higher affinity than SARS-CoV-2, while the bat isolate RaTG13 binds with two orders of magnitude lower affinity, consistent with prior reports (Shang et al., 2020; Wrobel et al., 2020).”
• Molecular Architecture of the SARS-CoV-2 Virus (2020, neutral): “The S protein binds to the cellular surface receptor angiotensin-converting enzyme 2 (ACE2) through the receptor binding domain (RBD), an essential step for membrane fusion (Hoffmann et al., 2020; Lan et al., 2020; Shang et al., 2020; Wang et al., 2020; Yan et al., 2020; Zhou et al., 2020).”