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Identification of a novel lineage bat SARS-related coronaviruses that use bat ACE2 receptor

Hua Guo, Ben Hu, Hao-rui Si, Yan Zhu, Wei Zhang, Bei Li, Ang Li, Rong Geng, Hao-Feng Lin, Xing-Lou Yang, Peng Zhou, Zheng-Li Shi
doi: https://doi.org/10.1101/2021.05.21.445091
Hua Guo
aCAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China
bUniversity of Chinese Academy of Sciences, Beijing, 100049, China
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Ben Hu
aCAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China
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Hao-rui Si
aCAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China
bUniversity of Chinese Academy of Sciences, Beijing, 100049, China
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Yan Zhu
aCAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China
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Wei Zhang
aCAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China
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Bei Li
aCAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China
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Ang Li
aCAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China
bUniversity of Chinese Academy of Sciences, Beijing, 100049, China
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Rong Geng
aCAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China
bUniversity of Chinese Academy of Sciences, Beijing, 100049, China
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Hao-Feng Lin
aCAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China
bUniversity of Chinese Academy of Sciences, Beijing, 100049, China
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Xing-Lou Yang
aCAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China
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Peng Zhou
aCAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China
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  • For correspondence: peng.zhou@wh.iov.cn zlshi@wh.iov.cn
Zheng-Li Shi
aCAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China
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  • For correspondence: peng.zhou@wh.iov.cn zlshi@wh.iov.cn
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Abstract

Severe respiratory disease coronavirus-2 (SARS-CoV-2) causes the most devastating disease, COVID-19, of the recent century. One of the unsolved scientific questions around SARS-CoV-2 is the animal origin of this virus. Bats and pangolins are recognized as the most probable reservoir hosts that harbor the highly similar SARS-CoV-2 related viruses (SARSr-CoV-2). Here, we report the identification of a novel lineage of SARSr-CoVs, including RaTG15 and seven other viruses, from bats at the same location where we found RaTG13 in 2015. Although RaTG15 and the related viruses share 97.2% amino acid sequence identities to SARS-CoV-2 in the conserved ORF1b region, but only show less than 77.6% to all known SARSr-CoVs in genome level, thus forms a distinct lineage in the Sarbecovirus phylogenetic tree. We then found that RaTG15 receptor binding domain (RBD) can bind to and use Rhinolophus affinis bat ACE2 (RaACE2) but not human ACE2 as entry receptor, although which contains a short deletion and has different key residues responsible for ACE2 binding. In addition, we show that none of the known viruses in bat SARSr-CoV-2 lineage or the novel lineage discovered so far use human ACE2 efficiently compared to SARSr-CoV-2 from pangolin or some of the SARSr-CoV-1 lineage viruses. Collectively, we suggest more systematic and longitudinal work in bats to prevent future spillover events caused by SARSr-CoVs or to better understand the origin of SARS-CoV-2.

Competing Interest Statement

The authors have declared no competing interest.

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Posted May 21, 2021.
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Identification of a novel lineage bat SARS-related coronaviruses that use bat ACE2 receptor
Hua Guo, Ben Hu, Hao-rui Si, Yan Zhu, Wei Zhang, Bei Li, Ang Li, Rong Geng, Hao-Feng Lin, Xing-Lou Yang, Peng Zhou, Zheng-Li Shi
bioRxiv 2021.05.21.445091; doi: https://doi.org/10.1101/2021.05.21.445091
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Identification of a novel lineage bat SARS-related coronaviruses that use bat ACE2 receptor
Hua Guo, Ben Hu, Hao-rui Si, Yan Zhu, Wei Zhang, Bei Li, Ang Li, Rong Geng, Hao-Feng Lin, Xing-Lou Yang, Peng Zhou, Zheng-Li Shi
bioRxiv 2021.05.21.445091; doi: https://doi.org/10.1101/2021.05.21.445091

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