OmniVira

Literature detail

Broader-species receptor binding and structural bases of Omicron SARS-CoV-2 to both mouse and palm-civet ACE2s.

Linjie Li1,2 Pu Han1 Baihan Huang1 Yufeng Xie1,3 Weiwei Li1,2 Di Zhang1,4 Pengcheng Han1,5 Zepeng Xu1,4 Bin Bai1,2 Jingya Zhou1,2 Xinrui Kang1,2 Xiaomei Li6 Anqi Zheng1,2 Rong Zhang1,7 Shitong Qiao1,2 Xin Zhao1 Jianxun Qi1,2 Qihui Wang1,2 Kefang Liu8 George Fu Gao9,10
Affiliations 10 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. Faculty of Health Sciences, University of Macau, Macau, Macau SAR, China.
  5. School of Medicine, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China.
  6. Cryo-EM Center, Shanxi Academy of Advanced Research and Innovation, Taiyuan, Shanxi, China.
  7. State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, Guangxi, China.
  8. CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. [email protected].
  9. CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. [email protected].
  10. University of Chinese Academy of Sciences, Beijing, China. [email protected].
PMID 35821014 2022 Cell Discov eng epublish
PubMed DOI Browse context

Article

Publication summary

The Omicron variant of SARS-CoV-2 carries multiple unusual mutations, particularly in the receptor-binding domain (RBD) of the spike (S) protein. Moreover, host-adapting mutations, such as residues 493, 498, and 501, were also observed in the Omicron RBD, which indicates that it is necessary to evaluate the interspecies transmission risk of the Omicron variant. Herein, we evaluated the interspecies recognition of the Omicron BA.1 and Delta RBDs by 27 ACE2 orthologs, including humans. We found that Omicron BA.1 expanded its receptor binding spectra to palm-civet, rodents, more bats (least horseshoe bat and greater horseshoe bat) and lesser hedgehog tenrec. Additionally, we determined the cryo-electron microscopy (cryo-EM) structure of the Omicron BA.1 S protein complexed with mouse ACE2 (mACE2) and the crystal structure of Omicron RBD complexed with palm-civet ACE2 (cvACE2). Several key residues for the host range have been identified. These results suggest that surveillance should be enhanced on the Omicron variant for its broader-species receptor binding to prevent spillover and expansion of reservoir hosts for a prolonged pandemic.

Structured evidence records

Evidence records

6 total
Host Range Experiment 2 records
Host Range Experiment Extraction confidence 0.90
Key finding

Omicron SARS-CoV-2 binds both mouse and palm-civet ACE2, showing expanded receptor usage confirmed by structural analysis.

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

We evaluated the interspecies recognition of the Omicron BA.1 and Delta RBDs by 27 ACE2 orthologs, including humans. We found that Omicron BA.1 expanded its receptor binding spectra to palm-civet, rodents, more bats (least horseshoe bat and greater horseshoe bat) and lesser hedgehog tenrec. Additionally, we determined the cryo-electron microscopy (cryo-EM) structure of the Omicron BA.1 S protein complexed with mouse ACE2 (mACE2) and the crystal structure of Omicron RBD complexed with palm-civet ACE2 (cvACE2).

Method
receptor binding assay; cryo-electron microscopy; crystal structure determination
Experimental system
in vitro cell-entry assay
Host Range Experiment Extraction confidence 0.90
Key finding

Omicron SARS-CoV-2 spike RBD binds to palm-civet ACE2, elucidated by crystal structure analysis.

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

Additionally, we determined the crystal structure of Omicron RBD complexed with palm-civet ACE2 (cvACE2).

Method
receptor binding assay; crystal structure determination
Experimental system
in vitro cell-entry assay
Receptor Usage 2 records
Receptor Usage Extraction confidence 0.98
Key finding

Omicron BA.1 variant of SARS-CoV-2 binds mouse ACE2 as shown by cryo-EM structural analysis of the Omicron spike protein in complex with mACE2.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

We found that Omicron BA.1 expanded its receptor binding spectra to palm-civet, rodents, more bats and lesser hedgehog tenrec. Additionally, we determined the cryo-EM structure of the Omicron BA.1 S protein complexed with mouse ACE2 (mACE2).

Method
cryo-electron microscopy
Receptors
ACE2
Receptor Usage Extraction confidence 0.98
Key finding

Omicron RBD binds to palm-civet ACE2 as demonstrated by the crystal structure of the Omicron RBD–cvACE2 complex.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

We determined the crystal structure of Omicron RBD complexed with palm-civet ACE2 (cvACE2).

Method
crystal structure determination
Receptors
ACE2
Cross Species Transmission 1 records
Cross Species Transmission Extraction confidence 0.80
Key finding

Omicron SARS-CoV-2 binds both mouse and palm-civet ACE2, indicating potential cross-species transmission among non-human mammals.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

We found that Omicron BA.1 expanded its receptor binding spectra to palm-civet, rodents, more bats (least horseshoe bat and greater horseshoe bat) and lesser hedgehog tenrec. Additionally, we determined the cryo-electron microscopy (cryo-EM) structure of the Omicron BA.1 S protein complexed with mouse ACE2 (mACE2) and the crystal structure of Omicron RBD complexed with palm-civet ACE2 (cvACE2).

Method
cryo-electron microscopy; crystal structure determination
Study design
structural analysis
Transmission direction
animal-to-animal
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

Omicron SARS-CoV-2 contains mutations at residues 493, 498, and 501 in the spike RBD that enable receptor binding and structural adaptation to mouse and palm-civet ACE2, expanding the host range.

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

The Omicron variant of SARS-CoV-2 carries multiple unusual mutations, particularly in the receptor-binding domain (RBD) of the spike (S) protein. Host-adapting mutations, such as residues 493, 498, and 501, were also observed in the Omicron RBD. We found that Omicron BA.1 expanded its receptor binding spectra to palm-civet and rodents, and determined the structures of Omicron S protein complexed with mouse ACE2 and RBD complexed with palm-civet ACE2.

Genes or proteins
spike; RBD
Receptors
ACE2
Mutations
residue 493; residue 498; residue 501
Mechanism types
receptor_binding; host_range_expansion