Cell
Volume 181, Issue 4, 14 May 2020, Pages 894-904.e9
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Article
Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2

https://doi.org/10.1016/j.cell.2020.03.045Get rights and content
open access

Highlights

  • SARS-CoV-2 interacts with hACE2 via S protein CTD

  • A 2.5-Å structure of SARS-CoV-2-CTD in complex with hACE2 is resolved

  • The SARS-CoV-2-CTD displays stronger affinity for hACE2 compared with SARS-RBD

  • SARS-CoV-2 -CTD is antigenically different from SARS-RBD

Summary

The recent emergence of a novel coronavirus (SARS-CoV-2) in China has caused significant public health concerns. Recently, ACE2 was reported as an entry receptor for SARS-CoV-2. In this study, we present the crystal structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) spike (S) protein in complex with human ACE2 (hACE2), which reveals a hACE2-binding mode similar overall to that observed for SARS-CoV. However, atomic details at the binding interface demonstrate that key residue substitutions in SARS-CoV-2-CTD slightly strengthen the interaction and lead to higher affinity for receptor binding than SARS-RBD. Additionally, a panel of murine monoclonal antibodies (mAbs) and polyclonal antibodies (pAbs) against SARS-CoV-S1/receptor-binding domain (RBD) were unable to interact with the SARS-CoV-2 S protein, indicating notable differences in antigenicity between SARS-CoV and SARS-CoV-2. These findings shed light on the viral pathogenesis and provide important structural information regarding development of therapeutic countermeasures against the emerging virus.

Keywords

SARS-CoV-2
CTD
receptor binding domain
receptor
ACE2
crystal structure
immunogenicity

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15

These authors contributed equally

16

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