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

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 repor...

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Published inCurrent biology Vol. 30; no. 11; pp. 2196 - 2203.e3
Main Authors Zhou, Hong, Chen, Xing, Hu, Tao, Li, Juan, Song, Hao, Liu, Yanran, Wang, Peihan, Liu, Di, Yang, Jing, Holmes, Edward C., Hughes, Alice C., Bi, Yuhai, Shi, Weifeng
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LanguageEnglish
Published England Elsevier Inc 08.06.2020
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Abstract 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. •Metagenomic analysis identified a novel coronavirus, RmYN02, from R. malayanus•RmYN02 was the closest relative of SARS-CoV-2 in most of the virus genome•Two loop deletions in RBD may reduce the binding of RmYN02 with ACE2•RmYN02 contains an insertion at the S1/S2 cleavage site in the spike protein Zhou et al. report a bat-derived coronavirus, RmYN02, which is the closest relative of SARS-CoV-2 in most of the virus genome reported to date. RmYN02 contains an insertion at the S1/S2 cleavage site in the spike protein in a similar manner to SARS-CoV-2. This suggests that such insertion events can occur naturally in animal betacoronaviruses.
AbstractList 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.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.
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. •Metagenomic analysis identified a novel coronavirus, RmYN02, from R. malayanus•RmYN02 was the closest relative of SARS-CoV-2 in most of the virus genome•Two loop deletions in RBD may reduce the binding of RmYN02 with ACE2•RmYN02 contains an insertion at the S1/S2 cleavage site in the spike protein Zhou et al. report a bat-derived coronavirus, RmYN02, which is the closest relative of SARS-CoV-2 in most of the virus genome reported to date. RmYN02 contains an insertion at the S1/S2 cleavage site in the spike protein in a similar manner to SARS-CoV-2. This suggests that such insertion events can occur naturally in animal betacoronaviruses.
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.
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. • Metagenomic analysis identified a novel coronavirus, RmYN02, from R. malayanus • RmYN02 was the closest relative of SARS-CoV-2 in most of the virus genome • Two loop deletions in RBD may reduce the binding of RmYN02 with ACE2 • RmYN02 contains an insertion at the S1/S2 cleavage site in the spike protein Zhou et al. report a bat-derived coronavirus, RmYN02, which is the closest relative of SARS-CoV-2 in most of the virus genome reported to date. RmYN02 contains an insertion at the S1/S2 cleavage site in the spike protein in a similar manner to SARS-CoV-2. This suggests that such insertion events can occur naturally in animal betacoronaviruses.
Author Hu, Tao
Wang, Peihan
Chen, Xing
Li, Juan
Holmes, Edward C.
Song, Hao
Bi, Yuhai
Shi, Weifeng
Liu, Yanran
Yang, Jing
Liu, Di
Hughes, Alice C.
Zhou, Hong
Author_xml – sequence: 1
  givenname: Hong
  surname: Zhou
  fullname: Zhou, Hong
  organization: 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
– sequence: 2
  givenname: Xing
  surname: Chen
  fullname: Chen, Xing
  organization: Landscape Ecology Group, Center for Integrative Conservation, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Menglun, Mengla, Yunnan 666303, China
– sequence: 3
  givenname: Tao
  surname: Hu
  fullname: Hu, Tao
  organization: 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
– sequence: 4
  givenname: Juan
  surname: Li
  fullname: Li, Juan
  organization: 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
– sequence: 5
  givenname: Hao
  surname: Song
  fullname: Song, Hao
  organization: Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China
– sequence: 6
  givenname: Yanran
  surname: Liu
  fullname: Liu, Yanran
  organization: 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
– sequence: 7
  givenname: Peihan
  surname: Wang
  fullname: Wang, Peihan
  organization: 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
– sequence: 8
  givenname: Di
  surname: Liu
  fullname: Liu, Di
  organization: Computational Virology Group, Center for Bacteria and Virus Resources and Bioinformation, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China
– sequence: 9
  givenname: Jing
  surname: Yang
  fullname: Yang, Jing
  organization: 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
– sequence: 10
  givenname: Edward C.
  surname: Holmes
  fullname: Holmes, Edward C.
  organization: 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
– sequence: 11
  givenname: Alice C.
  surname: Hughes
  fullname: Hughes, Alice C.
  email: ach_conservation2@hotmail.com
  organization: Landscape Ecology Group, Center for Integrative Conservation, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Menglun, Mengla, Yunnan 666303, China
– sequence: 12
  givenname: Yuhai
  surname: Bi
  fullname: Bi, Yuhai
  email: beeyh@im.ac.cn
  organization: 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
– sequence: 13
  givenname: Weifeng
  surname: Shi
  fullname: Shi, Weifeng
  email: shiwf@ioz.ac.cn
  organization: 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
BackLink https://www.ncbi.nlm.nih.gov/pubmed/32416074$$D View this record in MEDLINE/PubMed
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Keywords COVID-19
SARS-CoV-2
bat coronavirus
S1/S2 cleavage site
spike protein
Language English
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Snippet 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...
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 [...
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SubjectTerms Amino Acid Sequence
Animals
bat coronavirus
Betacoronavirus - chemistry
Betacoronavirus - genetics
Betacoronavirus - isolation & purification
Chiroptera - virology
COVID-19
Eutheria - virology
Feces - virology
Genome, Viral
Models, Molecular
Mutagenesis, Insertional
Phylogeny
RNA, Viral - genetics
S1/S2 cleavage site
SARS Virus - genetics
SARS-CoV-2
Sequence Alignment
Sequence Analysis, RNA
Spike Glycoprotein, Coronavirus - chemistry
Spike Glycoprotein, Coronavirus - genetics
spike protein
Title A Novel Bat Coronavirus Closely Related to SARS-CoV-2 Contains Natural Insertions at the S1/S2 Cleavage Site of the Spike Protein
URI https://dx.doi.org/10.1016/j.cub.2020.05.023
https://www.ncbi.nlm.nih.gov/pubmed/32416074
https://www.proquest.com/docview/2404042224
https://pubmed.ncbi.nlm.nih.gov/PMC7211627
Volume 30
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