The molecular basis for SARS-CoV-2 binding to dog ACE2

Zengyuan Zhang, Yanfang Zhang, Kefang Liu, Yan Li, Qiong Lu, Qingling Wang, Yuqin Zhang, Liang Wang, Hanyi Liao, Anqi Zheng, Sufang Ma, Zheng Fan, Huifang Li, Weijin Huang, Yuhai Bi, Xin Zhao, Qihui Wang, George F. Gao (), Haixia Xiao (), Zhou Tong (), Jianxun Qi () and Yeping Sun ()
Additional contact information
Zengyuan Zhang: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Yanfang Zhang: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Kefang Liu: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Yan Li: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Qiong Lu: Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, National Institutes for Food and Drug Control (NIFDC)
Qingling Wang: Northwest University
Yuqin Zhang: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Liang Wang: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Hanyi Liao: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Anqi Zheng: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Sufang Ma: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Zheng Fan: Institute of Microbiology, Chinese Academy of Sciences
Huifang Li: The Northern Medical District of the PLA General Hospital
Weijin Huang: Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, National Institutes for Food and Drug Control (NIFDC)
Yuhai Bi: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Xin Zhao: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Qihui Wang: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
George F. Gao: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Haixia Xiao: Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences
Zhou Tong: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Jianxun Qi: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Yeping Sun: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: Abstract SARS-CoV-2 can infect many domestic animals, including dogs. Herein, we show that dog angiotensin-converting enzyme 2 (dACE2) can bind to the SARS-CoV-2 spike (S) protein receptor binding domain (RBD), and that both pseudotyped and authentic SARS-CoV-2 can infect dACE2-expressing cells. We solved the crystal structure of RBD in complex with dACE2 and found that the total number of contact residues, contact atoms, hydrogen bonds and salt bridges at the binding interface in this complex are slightly fewer than those in the complex of the RBD and human ACE2 (hACE2). This result is consistent with the fact that the binding affinity of RBD to dACE2 is lower than that of hACE2. We further show that a few important mutations in the RBD binding interface play a pivotal role in the binding affinity of RBD to both dACE2 and hACE2. Our work reveals a molecular basis for cross-species transmission and potential animal spread of SARS-CoV-2, and provides new clues to block the potential transmission chains of this virus.

Date: 2021
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DOI: 10.1038/s41467-021-24326-y

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