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Literature detail

Binding and structural basis of equine ACE2 to RBDs from SARS-CoV, SARS-CoV-2 and related coronaviruses.

Zepeng Xu1,2 Xinrui Kang1,3 Pu Han1 Pei Du1 Linjie Li1,4 Anqi Zheng1,4 Chuxia Deng2 Jianxun Qi1,4 Xin Zhao1 Qihui Wang5,6 Kefang Liu7 George Fu Gao1
Affiliations 7 institutions
  1. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
  2. Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China.
  3. Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 100049, China.
  4. University of Chinese Academy of Sciences, Beijing, 100049, China.
  5. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. [email protected].
  6. University of Chinese Academy of Sciences, Beijing, 100049, China. [email protected].
  7. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. [email protected].
PMID 35729237 2022 Nat Commun eng epublish
PubMed DOI Browse context

Article

Publication summary

The origin and host range of SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), are important scientific questions as they might provide insight into understanding of the potential future spillover to infect humans. Here, we tested the binding between equine angiotensin converting enzyme 2 (eqACE2) and the receptor binding domains (RBDs) of SARS-CoV, SARS-CoV-2 prototype (PT) and variant of concerns (VOCs), as well as their close relatives bat-origin coronavirus (CoV) RaTG13 and pangolin-origin CoVs GX/P2V/2017 and GD/1/2019. We also determined the crystal structures of eqACE2/RaTG13-RBD, eqACE2/SARS-CoV-2 PT-RBD and eqACE2/Omicron BA.1-RBD. We identified S494 of SARS-COV-2 PT-RBD as an important residue in the eqACE2/SARS-COV-2 PT-RBD interaction and found that N501Y, the commonly recognized enhancing mutation, attenuated the binding affinity with eqACE2. Our work demonstrates that horses are potential targets for SARS-CoV-2 and highlights the importance of continuous surveillance on SARS-CoV-2 and related CoVs to prevent spillover events.

Angiotensin-Converting Enzyme 2 COVID-19 Animals Horses Peptidyl-Dipeptidase A Protein Binding SARS-CoV-2 Spike Glycoprotein, Coronavirus spike protein, SARS-CoV-2

Structured evidence records

Evidence records

5 total
Receptor Usage 4 records
Receptor Usage Extraction confidence 1.00
Key finding

Equine ACE2 bound to the RBDs of SARS-CoV, SARS-CoV-2 variants, and related bat and pangolin coronaviruses, showing receptor compatibility with horses.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

We tested the binding between equine angiotensin converting enzyme 2 (eqACE2) and the receptor binding domains (RBDs) of SARS-CoV, SARS-CoV-2 prototype (PT) and variant of concerns (VOCs), as well as their close relatives bat-origin CoV RaTG13 and pangolin-origin CoVs GX/P2V/2017 and GD/1/2019.

Method
binding assay; structural analysis
Receptors
ACE2
Receptor Usage Extraction confidence 1.00
Key finding

Equine ACE2 showed detectable binding with the SARS-CoV receptor-binding domain, indicating potential receptor usage in horses.

Virus
SARS-CoV
Location
Not specified
Supporting text

We tested the binding between equine angiotensin converting enzyme 2 (eqACE2) and the receptor binding domains (RBDs) of SARS-CoV, SARS-CoV-2 prototype (PT) and variant of concerns (VOCs), as well as their close relatives bat-origin CoV RaTG13 and pangolin-origin CoVs GX/P2V/2017 and GD/1/2019.

Method
binding assay; structural analysis
Receptors
ACE2
Receptor Usage Extraction confidence 1.00
Key finding

Equine ACE2 bound to the RaTG13 receptor-binding domain, showing receptor compatibility between horse ACE2 and the bat-origin coronavirus.

Virus
SARSr-CoV
Location
Not specified
Supporting text

We tested the binding between equine angiotensin converting enzyme 2 (eqACE2) and the receptor binding domains (RBDs) of SARS-CoV, SARS-CoV-2 prototype (PT) and variant of concerns (VOCs), as well as their close relatives bat-origin CoV RaTG13 and pangolin-origin CoVs GX/P2V/2017 and GD/1/2019.

Method
binding assay; structural analysis
Receptors
ACE2
Receptor Usage Extraction confidence 1.00
Key finding

Equine ACE2 bound to the receptor-binding domains of pangolin-origin coronaviruses GX/P2V/2017 and GD/1/2019, demonstrating receptor-mediated compatibility.

Virus
SARSr-CoV
Location
Not specified
Supporting text

We tested the binding between equine angiotensin converting enzyme 2 (eqACE2) and the receptor binding domains (RBDs) of SARS-CoV, SARS-CoV-2 prototype (PT) and variant of concerns (VOCs), as well as their close relatives bat-origin CoV RaTG13 and pangolin-origin CoVs GX/P2V/2017 and GD/1/2019.

Method
binding assay; structural analysis
Receptors
ACE2
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

S494 contributes to SARS-CoV-2 prototype RBD interaction with equine ACE2, while the N501Y mutation reduces binding affinity, indicating mutation-dependent adaptation influencing cross-species receptor usage.

Virus
SARS-CoV-2
Host
Not specified
Location
Not specified
Supporting text

We identified S494 of SARS-COV-2 PT-RBD as an important residue in the eqACE2/SARS-COV-2 PT-RBD interaction and found that N501Y, the commonly recognized enhancing mutation, attenuated the binding affinity with eqACE2.

Genes or proteins
Spike; RBD
Receptors
ACE2; equine ACE2
Mutations
S494; N501Y
Mechanism types
receptor_binding; host_range_adaptation