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Literature detail

A Novel Bat Coronavirus Closely Related to SARS-CoV-2 Contains Natural Insertions at the S1/S2 Cleavage Site of the Spike Protein.

Hong Zhou1 Xing Chen2 Tao Hu1 Juan Li1 Hao Song3 Yanran Liu1 Peihan Wang1 Di Liu4 Jing Yang5 Edward C Holmes6 Alice C Hughes7 Yuhai Bi8 Weifeng Shi9,10
Affiliations 10 institutions
  1. Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University, and Shandong Academy of Medical Sciences, Taian 271000, China.
  2. Landscape Ecology Group, Center for Integrative Conservation, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Menglun, Mengla, Yunnan 666303, China.
  3. Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
  4. Computational Virology Group, Center for Bacteria and Virus Resources and Bioinformation, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
  5. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, CAS Center for Influenza Research and Early-Warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing 100101, China.
  6. Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and School of Medical Sciences, The University of Sydney, Sydney, NSW 2006, Australia.
  7. Landscape Ecology Group, Center for Integrative Conservation, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Menglun, Mengla, Yunnan 666303, China. Electronic address: [email protected].
  8. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, CAS Center for Influenza Research and Early-Warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing 100101, China. Electronic address: [email protected].
  9. Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University, and Shandong Academy of Medical Sciences, Taian 271000, China
  10. The First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital), Ji'nan 250014, China. Electronic address: [email protected].
PMID 32416074 2020 Curr Biol eng ppublish
PubMed DOI Browse context

Article

Publication summary

The unprecedented pandemic of pneumonia caused by a novel coronavirus, SARS-CoV-2, in China and beyond has had major public health impacts on a global scale [1, 2]. Although bats are regarded as the most likely natural hosts for SARS-CoV-2 [3], the origins of the virus remain unclear. Here, we report a novel bat-derived coronavirus, denoted RmYN02, identified from a metagenomic analysis of samples from 227 bats collected from Yunnan Province in China between May and October 2019. Notably, RmYN02 shares 93.3% nucleotide identity with SARS-CoV-2 at the scale of the complete virus genome and 97.2% identity in the 1ab gene, in which it is the closest relative of SARS-CoV-2 reported to date. In contrast, RmYN02 showed low sequence identity (61.3%) to SARS-CoV-2 in the receptor-binding domain (RBD) and might not bind to angiotensin-converting enzyme 2 (ACE2). Critically, and in a similar manner to SARS-CoV-2, RmYN02 was characterized by the insertion of multiple amino acids at the junction site of the S1 and S2 subunits of the spike (S) protein. This provides strong evidence that such insertion events can occur naturally in animal betacoronaviruses.

bat coronavirus COVID-19 S1/S2 cleavage site SARS-CoV-2 spike protein Mutagenesis, Insertional Amino Acid Sequence Animals Betacoronavirus Chiroptera Eutheria Feces Genome, Viral Models, Molecular Phylogeny RNA, Viral SARS-CoV-2 Sequence Alignment

Structured evidence records

Evidence records

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

RmYN02, a bat coronavirus closely related to SARS-CoV-2, exhibits natural amino acid insertions at the S1/S2 cleavage site of the spike protein, demonstrating a molecular adaptation mechanism similar to that of SARS-CoV-2.

Virus
SARSr-CoV
Host
Not specified
Location
Not specified
Supporting text

Critically, and in a similar manner to SARS-CoV-2, RmYN02 was characterized by the insertion of multiple amino acids at the junction site of the S1 and S2 subunits of the spike (S) protein. This provides strong evidence that such insertion events can occur naturally in animal betacoronaviruses.

Genes or proteins
spike; S1; S2
Mutations
amino acid insertions at S1/S2 cleavage site
Mechanism types
cell_entry; receptor_binding
Molecular Adaptation Extraction confidence 0.85
Key finding

RmYN02’s receptor-binding domain has low similarity to SARS-CoV-2 and may lack ACE2 binding, indicating molecular divergence in receptor interaction.

Virus
SARSr-CoV
Host
Not specified
Location
Not specified
Supporting text

RmYN02 showed low sequence identity (61.3%) to SARS-CoV-2 in the receptor-binding domain (RBD) and might not bind to angiotensin-converting enzyme 2 (ACE2).

Genes or proteins
receptor-binding domain; spike
Receptors
ACE2
Mechanism types
receptor_binding
Genomic Evolution 1 records
Genomic Evolution Extraction confidence 0.95
Key finding

Metagenomic and phylogenetic analyses identified a novel bat coronavirus, RmYN02, with high genome similarity to SARS-CoV-2 and natural insertions at the S1/S2 site of the spike protein, indicating natural molecular evolution in bat betacoronaviruses.

Virus
SARSr-CoV
Host
Chiroptera
Location
Not specified
Supporting text

Here, we report a novel bat-derived coronavirus, denoted RmYN02, identified from a metagenomic analysis of samples from 227 bats collected from Yunnan Province in China between May and October 2019. Notably, RmYN02 shares 93.3% nucleotide identity with SARS-CoV-2 at the scale of the complete virus genome and 97.2% identity in the 1ab gene, in which it is the closest relative of SARS-CoV-2 reported to date. Critically, and in a similar manner to SARS-CoV-2, RmYN02 was characterized by the insertion of multiple amino acids at the junction site of the S1 and S2 subunits of the spike (S) protein.

Genes or proteins
1ab; spike protein; S1/S2 cleavage site
Analysis methods
metagenomic analysis; phylogenetic analysis; sequence identity comparison
Zoonotic Surveillance 1 records
Zoonotic Surveillance Extraction confidence 1.00
Key finding

Metagenomic analysis of bat samples from Yunnan Province, China, detected the novel coronavirus RmYN02 closely related to SARS-CoV-2.

Virus
SARSr-CoV
Host
Chiroptera
Location
China Yunnan Province, China
Supporting text

A novel bat-derived coronavirus, denoted RmYN02, identified from a metagenomic analysis of samples from 227 bats collected from Yunnan Province in China between May and October 2019.

Method
metagenomic analysis
Geographic raw
Yunnan Province
Country inferred
China