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Literature detail

Structural basis of white-tailed deer, <i>Odocoileus virginianus</i>, ACE2 recognizing all the SARS-CoV-2 variants of concern with high affinity.

Pu Han1 Yumin Meng1,2 Di Zhang1,3 Zepeng Xu1,3 Zhiyuan Li4 Xiaoqian Pan1,2 Zhennan Zhao1 Linjie Li1 Lingfeng Tang1,3 Jianxun Qi1,2 Kefang Liu1,5 George F Gao1,2
Affiliations 5 institutions
  1. CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS) , Beijing, China.
  2. University of Chinese Academy of Sciences , Beijing, China.
  3. Faculty of Health Sciences, University of Macau , Macau SAR, China.
  4. College of Veterinary Medicine, China Agricultural University , Beijing, China.
  5. Beijing Life Science Academy , Beijing, China.
PMID 37676003 2023 J Virol eng ppublish
PubMed DOI Browse context

Article

Publication summary

SARS-CoV-2 has been expanding its host range, among which the white-tailed deer (WTD), <i>Odocoileus virginianus,</i> became the first wildlife species infected on a large scale and might serve as a host reservoir for variants of concern (VOCs) in case no longer circulating in humans. In this study, we comprehensively assessed the binding of the WTD angiotensin-converting enzyme 2 (ACE2) receptor to the spike (S) receptor-binding domains (RBDs) from the SARS-CoV-2 prototype (PT) strain and multiple variants. We found that WTD ACE2 could be broadly recognized by all of the tested RBDs. We further determined the complex structures of WTD ACE2 with PT, Omicron BA.1, and BA.4/5 S trimer. Detailed structural comparison revealed the important roles of RBD residues on 486, 498, and 501 sites for WTD ACE2 binding. This study deepens our understanding of the interspecies transmission mechanisms of SARS-CoV-2 and further addresses the importance of constant monitoring on SARS-CoV-2 infections in wild animals. IMPORTANCE Even if we manage to eliminate the virus among humans, it will still circulate among wildlife and continuously be transmitted back to humans. A recent study indicated that WTD may serve as reservoir for nearly extinct SARS-CoV-2 strains. Therefore, it is critical to evaluate the binding abilities of SARS-CoV-2 variants to the WTD ACE2 receptor and elucidate the molecular mechanisms of binding of the RBDs to assess the risk of spillback events.

ACE2 cryo-EM structure Odocoileus virginianus RBD S proteins SARS-CoV-2 white-tailed deer Angiotensin-Converting Enzyme 2 COVID-19 Deer SARS-CoV-2 Spike Glycoprotein, Coronavirus Animals Binding Sites Humans Protein Binding Protein Domains Receptors, Virus

Structured evidence records

Evidence records

2 total
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.90
Key finding

Mutations at residues 486, 498, and 501 within the SARS-CoV-2 spike RBD contribute to high-affinity binding to white-tailed deer ACE2, supporting viral adaptation to this host.

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

Detailed structural comparison revealed the important roles of RBD residues on 486, 498, and 501 sites for WTD ACE2 binding.

Genes or proteins
spike; RBD
Receptors
ACE2
Mutations
RBD 486; RBD 498; RBD 501
Mechanism types
receptor_binding; host_factor_interaction
Receptor Usage 1 records
Receptor Usage Extraction confidence 1.00
Key finding

White-tailed deer ACE2 receptor binds SARS-CoV-2 spike RBDs from prototype and variant strains with high affinity, with residues 486, 498, and 501 mediating receptor interaction.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

We comprehensively assessed the binding of the WTD angiotensin-converting enzyme 2 (ACE2) receptor to the spike (S) receptor-binding domains (RBDs) from the SARS-CoV-2 prototype (PT) strain and multiple variants. We found that WTD ACE2 could be broadly recognized by all of the tested RBDs. Detailed structural comparison revealed the important roles of RBD residues on 486, 498, and 501 sites for WTD ACE2 binding.

Method
binding assay; structural analysis; cryo-EM structure determination
Receptors
ACE2