OmniVira

Genomic and structural evidence of SARS-CoV-2 and MERS-CoV in migratory birds.

Jian Cao1,2 Sheng Liu3,4 Chao Su1 Liang Wang1 Zhiyuan Li1 Jianxun Qi1,2 Peiyi Wang4 George F Gao1
Affiliations 4 institutions
  1. Chinese Academy of Sciences Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  2. Beijing Life Science Academy, Beijing 102200, China.
  3. Institute of Pediatrics, Shenzhen Children's Hospital, Shenzhen 518026, China.
  4. Cryo-electron Microscopy Center, Department of Biology, Southern University of Science and Technology, Shenzhen 518055, China.
PMID42372155 DOI10.1073/pnas.2400023123 Year2026 Journal Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A Languageeng Statusppublish

Abstract

Migratory birds are the natural reservoir of influenza A virus (IAV), but their role as a carrier of SARS-CoV-2 remains unclear. Here, we report the identification of three almost full-length viral genome sequences of SARS-CoV-2 variants of concern (VOCs) in Tundra swans. These sequences are named hCoV-19/Tundra swan/Jiangxi/IMCAS_M1/2021 (IMCAS_M1), hCoV-19/Tundra swan/Jiangxi /IMCAS_M2/2021 (IMCAS_M2), and hCoV-19/Tundra swan/Jiangxi/IMCAS_M3/2021 (IMCAS_M3). IMCAS_M1 and IMCAS_M3 have the same mutations as the Beta VOC (K417N, E484K, and N501Y) in the receptor-binding domain (RBD) of the viral spike (S) protein, whereas IMCAS_M2 shares the same mutations as the Gamma VOC (K417T, E484K, and N501Y) in the RBD with all three showing their distinct mutations in the genomes. Virus receptor angiotensin-converting enzyme 2 (ACE2) proteins from both Tundra swan (tsACE2) and Black swan (bsACE2) can bind to the RBDs of all three viruses and the Alpha VOC, but not to RBD of the prototype (PT) virus. The polar contacts and hydrophobic interactions revealed by cryo-electron microscopy (cryo-EM) structures of the RBD-ACE2 complex, play key roles in virus-receptor engagement. Furthermore, HeLa cells expressing bsACE2 and tsACE2 proteins could be transduced by pseudotyped SARS-CoV-2 variants (Alpha, Beta, and Gamma) but not PT SARS-CoV-2. In addition, we obtained one partial genome of MERS-CoV named Bar-headed goose/Tibet/IMCAS_M4/2022 (IMCAS_M4) with 20,180 bp (~70.0% coverage). Our findings highlight the importance of migratory birds as potential carrier of both SARS-CoV-2 and MERS-CoV, thereby posing potential threat to public health.

Supporting text Virus Host Location
genome 8 MERS-CoV 24 migratory birds 5 SARS-CoV-2 550 Tundra swan 1 Animal Migration 21 Birds 212 COVID-19 425 Genome, Viral 317 Middle East Respiratory Syndrome Coronavirus 68 SARS-CoV-2 453 Animals 1948 Humans 1440 Mutation 209 Spike Glycoprotein, Coronavirus 274 spike protein, SARS-CoV-2 157

Evidence records

8 total
Zoonotic Surveillance
2 records · 1 evidence types
Evidence type Viral Detection
2 records
OVE11784 Viral Detection
Key finding

A partial MERS-CoV genome (~20,180 bp; ~70% coverage) was detected in a Bar-headed goose in Tibet.

Virus
Middle East Respiratory Syndrome Coronavirus
Host
Bar-headed goose Natural host
Location
China
Supporting text

In addition, we obtained one partial genome of MERS-CoV named Bar-headed goose/Tibet/IMCAS_M4/2022 (IMCAS_M4) with 20,180 bp (~70.0% coverage).

Method
genome sequencing
Geographic raw
Tibet
Country inferred
CHN
OVE11783 Viral Detection
Key finding

Nearly full-length SARS-CoV-2 genomes were detected in Tundra swans in Jiangxi.

Virus
Severe acute respiratory syndrome coronavirus 2
Host
Tundra swans Natural host
Location
China
Supporting text

Here, we report the identification of three almost full-length viral genome sequences of SARS-CoV-2 variants of concern (VOCs) in Tundra swans. These sequences are named hCoV-19/Tundra swan/Jiangxi/IMCAS_M1/2021 (IMCAS_M1), hCoV-19/Tundra swan/Jiangxi /IMCAS_M2/2021 (IMCAS_M2), and hCoV-19/Tundra swan/Jiangxi/IMCAS_M3/2021 (IMCAS_M3).

Method
genome sequencing
Geographic raw
Jiangxi
Country inferred
CHN
Experimental Infection
1 records · 1 evidence types
Evidence type Host Range Experiment
1 records
OVE11790 Host Range Experiment
Key finding

HeLa cells expressing Tundra swan or Black swan ACE2 were transduced by pseudotyped SARS-CoV-2 Alpha, Beta, and Gamma variants but not by prototype SARS-CoV-2.

Virus
Severe acute respiratory syndrome coronavirus 2
Host
HeLa cells expressing bsACE2 Experimental system HeLa cells expressing tsACE2 Experimental system
Location
Not specified
Supporting text

HeLa cells expressing bsACE2 and tsACE2 proteins could be transduced by pseudotyped SARS-CoV-2 variants (Alpha, Beta, and Gamma) but not PT SARS-CoV-2.

Method
pseudotyped virus transduction assay
Experimental system
pseudovirus entry assay in HeLa cells overexpressing Black swan (bsACE2) or Tundra swan (tsACE2) ACE2
Functional Mechanism
3 records · 1 evidence types
Evidence type Receptor Usage
3 records
OVE11787 Receptor Usage
Key finding

Tundra swan and Black swan ACE2 bind SARS-CoV-2 RBDs of Alpha, Beta, and Gamma variants but not the prototype virus.

Virus
Severe acute respiratory syndrome coronavirus 2
Host
Tundra swan Experimental system Black swan Experimental system
Location
Not specified
Supporting text

Virus receptor angiotensin-converting enzyme 2 (ACE2) proteins from both Tundra swan (tsACE2) and Black swan (bsACE2) can bind to the RBDs of all three viruses and the Alpha VOC, but not to RBD of the prototype (PT) virus.

Method
receptor-binding assay
Receptors
ACE2 | tsACE2 | bsACE2
OVE11788 Receptor Usage
Key finding

HeLa cells expressing Tundra swan or Black swan ACE2 are transduced by SARS-CoV-2 Alpha, Beta, and Gamma pseudoviruses but not prototype SARS-CoV-2.

Virus
Severe acute respiratory syndrome coronavirus 2
Host
HeLa cells expressing bsACE2 Experimental system HeLa cells expressing tsACE2 Experimental system
Location
Not specified
Supporting text

Furthermore, HeLa cells expressing bsACE2 and tsACE2 proteins could be transduced by pseudotyped SARS-CoV-2 variants (Alpha, Beta, and Gamma) but not PT SARS-CoV-2.

Method
pseudovirus transduction assay | heterologous ACE2 expression in HeLa cells
Receptors
ACE2 | tsACE2 | bsACE2
OVE11789 Receptor Usage
Key finding

Cryo-EM structures show polar contacts and hydrophobic interactions mediating engagement between swan ACE2 and SARS-CoV-2 RBD.

Virus
Severe acute respiratory syndrome coronavirus 2
Host
Not specified
Location
Not specified
Supporting text

The polar contacts and hydrophobic interactions revealed by cryo-electron microscopy (cryo-EM) structures of the RBD-ACE2 complex, play key roles in virus-receptor engagement.

Method
cryo-electron microscopy (cryo-EM) of RBD–ACE2 complex | structural analysis
Receptors
ACE2 | tsACE2 | bsACE2
Genomic Evolution
2 records · 1 evidence types
Evidence type Phylogenetic Evolution
2 records
OVE11785 Phylogenetic Evolution
Key finding

SARS-CoV-2 genomes IMCAS_M1 and IMCAS_M3 from Tundra swans carry the Beta VOC-characteristic RBD mutations K417N, E484K, and N501Y.

Virus
Severe acute respiratory syndrome coronavirus 2 IMCAS_M1 IMCAS_M3 Beta VOC
Host
Tundra swans Natural host
Location
Not specified
Supporting text

Here, we report the identification of three almost full-length viral genome sequences of SARS-CoV-2 variants of concern (VOCs) in Tundra swans. IMCAS_M1 and IMCAS_M3 have the same mutations as the Beta VOC (K417N, E484K, and N501Y) in the receptor-binding domain (RBD) of the viral spike (S) protein,

Genes or proteins
spike (S) protein | receptor-binding domain (RBD)
Analysis methods
comparative genomic mutation profiling
OVE11786 Phylogenetic Evolution
Key finding

The SARS-CoV-2 genome IMCAS_M2 from a Tundra swan possesses the Gamma VOC-characteristic RBD mutations K417T, E484K, and N501Y.

Virus
Severe acute respiratory syndrome coronavirus 2 IMCAS_M2 Gamma VOC
Host
Tundra swans Natural host
Location
Not specified
Supporting text

Here, we report the identification of three almost full-length viral genome sequences of SARS-CoV-2 variants of concern (VOCs) in Tundra swans. IMCAS_M2 shares the same mutations as the Gamma VOC (K417T, E484K, and N501Y) in the RBD

Genes or proteins
spike (S) protein | receptor-binding domain (RBD)
Analysis methods
comparative genomic mutation profiling