OmniVira

Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2.

Qihui Wang1,2,3 Yanfang Zhang4,5,6 Lili Wu1,7 Sheng Niu4,8 Chunli Song1,9 Zengyuan Zhang4,7 Guangwen Lu10 Chengpeng Qiao11 Yu Hu4,12 Kwok-Yung Yuen13,14 Qisheng Wang15 Huan Zhou15 Jinghua Yan1,2,4,16,17 Jianxun Qi4,18
Affiliations 18 institutions
  1. CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
  2. Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China
  3. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  4. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
  5. University of the Chinese Academy of Sciences, Beijing 100049, China
  6. Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Biotechnology, Tianjin 300308, China.
  7. University of the Chinese Academy of Sciences, Beijing 100049, China.
  8. College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China.
  9. Institute of Physical Science and Information, Anhui University, Hefei 230039, China.
  10. West China Hospital Emergency Department (WCHED), State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
  11. CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  12. School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China.
  13. State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China
  14. Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China.
  15. Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201204, China.
  16. Institute of Physical Science and Information, Anhui University, Hefei 230039, China
  17. College of Life Science, University of the Chinese Academy of Sciences, Beijing 100049, China. Electronic address: [email protected].
  18. Savaid Medical School, University of the Chinese Academy of Sciences, Beijing 100049, China. Electronic address: [email protected].
PMID32275855 DOI10.1016/j.cell.2020.03.045 Year2020 Journal Cell Languageeng Statusppublish

Abstract

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.

Supporting text Virus Host Location
ACE2 54 crystal structure 4 CTD 1 immunogenicity 1 receptor 18 receptor binding domain 7 SARS-CoV-2 550 Virus Internalization 100 Amino Acid Sequence 128 Angiotensin-Converting Enzyme 2 177 Betacoronavirus 78 Epitopes 17 Humans 1440 Models, Molecular 99 Peptidyl-Dipeptidase A 57 Phylogeny 805 Protein Domains 45 SARS-CoV-2 453 Sequence Alignment 51 Severe acute respiratory syndrome-related coronavirus 78 Spike Glycoprotein, Coronavirus 274 ACE2 protein, human 87 spike protein, SARS-CoV-2 157

Evidence records

1 total
Functional Mechanism
1 records · 1 evidence types
Evidence type Receptor Usage
1 records
OVE3723 Receptor Usage
Key finding

SARS-CoV-2 spike protein binds and uses human ACE2 as an entry receptor.

Virus
Severe acute respiratory syndrome coronavirus 2
Host
human Homo sapiens Experimental system
Location
Not specified
Supporting text

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).

Method
crystal structure determination | protein complex structural analysis
Receptors
ACE2 | human ACE2 (hACE2)