OmniVira

Literature detail

Structural basis for receptor binding and broader interspecies receptor recognition of currently circulating Omicron sub-variants.

Zhennan Zhao1,2 Yufeng Xie1,3 Bin Bai1,2 Chunliang Luo1,4 Jingya Zhou2,5 Weiwei Li1,2 Yumin Meng1,2 Linjie Li1,2 Dedong Li1 Xiaomei Li6 Xiaoxiong Li6 Xiaoyun Wang1 Junqing Sun1,4 Zepeng Xu1,7 Yeping Sun1 Wei Zhang1 Zheng Fan1 Xin Zhao1 Linhuan Wu8 Juncai Ma8 Odel Y Li9 Guijun Shang6 Yan Chai1 Kefang Liu10 Peiyi Wang11 George F Gao12,13,14 Jianxun Qi15,16,17
Affiliations 17 institutions
  1. CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  2. University of Chinese Academy of Sciences, Beijing, China.
  3. Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
  4. College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, China.
  5. Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.
  6. Shanxi Academy of Advanced Research and Innovation, Taiyuan, China.
  7. Faculty of Health Sciences, University of Macau, Macau, China.
  8. Chinese National Microbiology Data Center (NMDC), Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  9. NHC Key Laboratory of Parasite and Vector Biology, National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China.
  10. CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. [email protected].
  11. Cryo-EM Center, Department of Biology, Southern University of Science and Technology, Shenzhen, China. [email protected].
  12. CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. [email protected].
  13. University of Chinese Academy of Sciences, Beijing, China. [email protected].
  14. Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China. [email protected].
  15. CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. [email protected].
  16. University of Chinese Academy of Sciences, Beijing, China. [email protected].
  17. Beijing Life Science Academy, Beijing, China. [email protected].
PMID 37479708 2023 Nat Commun eng epublish
PubMed DOI Browse context

Article

Publication summary

Multiple SARS-CoV-2 Omicron sub-variants, such as BA.2, BA.2.12.1, BA.4, and BA.5, emerge one after another. BA.5 has become the dominant strain worldwide. Additionally, BA.2.75 is significantly increasing in some countries. Exploring their receptor binding and interspecies transmission risk is urgently needed. Herein, we examine the binding capacities of human and other 28 animal ACE2 orthologs covering nine orders towards S proteins of these sub-variants. The binding affinities between hACE2 and these sub-variants remain in the range as that of previous variants of concerns (VOCs) or interests (VOIs). Notably, R493Q reverse mutation enhances the bindings towards ACE2s from humans and many animals closely related to human life, suggesting an increased risk of cross-species transmission. Structures of S/hACE2 or RBD/hACE2 complexes for these sub-variants and BA.2 S binding to ACE2 of mouse, rat or golden hamster are determined to reveal the molecular basis for receptor binding and broader interspecies recognition.

Angiotensin-Converting Enzyme 2 COVID-19 Animals Cricetinae Humans Mesocricetus Mice Mutation Rats SARS-CoV-2

Structured evidence records

Evidence records

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

SARS-CoV-2 Omicron sub-variants, including BA.2, bind ACE2 receptors from human, mouse, rat, and golden hamster, revealing structural determinants of receptor recognition across species.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

Structures of S/hACE2 or RBD/hACE2 complexes for these sub-variants and BA.2 S binding to ACE2 of mouse, rat or golden hamster are determined to reveal the molecular basis for receptor binding and broader interspecies recognition.

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

SARS-CoV-2 Omicron sub-variant BA.2 binds ACE2 receptors from mouse, rat, and golden hamster, supporting cross-species receptor compatibility.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

Structures of S/hACE2 or RBD/hACE2 complexes for these sub-variants and BA.2 S binding to ACE2 of mouse, rat or golden hamster are determined to reveal the molecular basis for receptor binding and broader interspecies recognition.

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

The SARS-CoV-2 Omicron BA.2 spike protein binds ACE2 receptors derived from rats, indicating receptor-mediated compatibility beyond human hosts.

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

Structures of S/hACE2 or RBD/hACE2 complexes for these sub-variants and BA.2 S binding to ACE2 of mouse, rat or golden hamster are determined to reveal the molecular basis for receptor binding and broader interspecies recognition.

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

The SARS-CoV-2 Omicron BA.2 variant binds ACE2 receptors from golden hamster, revealing molecular basis of interspecies receptor recognition.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

Structures of S/hACE2 or RBD/hACE2 complexes for these sub-variants and BA.2 S binding to ACE2 of mouse, rat or golden hamster are determined to reveal the molecular basis for receptor binding and broader interspecies recognition.

Method
structural analysis
Receptors
ACE2
Cross Species Transmission 2 records
Cross Species Transmission Extraction confidence 0.90
Key finding

BA.2 spike protein binds ACE2 receptors from mouse, rat, and golden hamster, indicating potential cross-species transmission among these rodents.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

Structures of S/hACE2 or RBD/hACE2 complexes for these sub-variants and BA.2 S binding to ACE2 of mouse, rat or golden hamster are determined to reveal the molecular basis for receptor binding and broader interspecies recognition.

Method
protein complex structure determination; binding assay
Study design
structural analysis
Transmission direction
animal-to-animal
Cross Species Transmission Extraction confidence 0.90
Key finding

BA.2 spike protein binds ACE2 receptors from golden hamster, indicating potential cross-species transmission capacity between rodent species.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

Structures of S/hACE2 or RBD/hACE2 complexes for these sub-variants and BA.2 S binding to ACE2 of mouse, rat or golden hamster are determined to reveal the molecular basis for receptor binding and broader interspecies recognition.

Method
protein complex structure determination; binding assay
Study design
structural analysis
Transmission direction
animal-to-animal
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

The R493Q mutation in the SARS-CoV-2 Omicron sub-variants spike enhances binding to ACE2 receptors from humans and various animals, contributing to broader interspecies receptor recognition.

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

Notably, R493Q reverse mutation enhances the bindings towards ACE2s from humans and many animals closely related to human life, suggesting an increased risk of cross-species transmission.

Genes or proteins
spike
Receptors
ACE2
Mutations
R493Q
Mechanism types
receptor_binding; cross_species_recognition