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

Severe respiratory disease coronavirus-2 (SARS-CoV-2) has been the most devastating disease COVID-19 in the century. One of the unsolved scientific questions of SARS-CoV-2 is the animal origin of this virus. Bats and pangolins are recognized as the most probable reservoir hosts that harbour highly s...

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Main Authors: 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
Format: Article
Language:English
Published: Taylor & Francis Group 2021-01-01
Series:Emerging Microbes and Infections
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2021.1956373
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author 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
author_facet 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
author_sort Hua Guo
collection DOAJ
description Severe respiratory disease coronavirus-2 (SARS-CoV-2) has been the most devastating disease COVID-19 in the century. One of the unsolved scientific questions of SARS-CoV-2 is the animal origin of this virus. Bats and pangolins are recognized as the most probable reservoir hosts that harbour highly similar SARS-CoV-2 related viruses (SARSr-CoV-2). This study identified 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 with SARS-CoV-2 in the conserved ORF1b region, it only shows less than 77.6% nucleotide identity to all known SARSr-CoVs at the genome level, thus forming a distinct lineage in the Sarbecovirus phylogenetic tree. We found that the RaTG15 receptor-binding domain (RBD) can bind to ACE2 from Rhinolophus affinis, Malayan pangolin, and use it as an entry receptor, except for ACE2 from humans. However, it contains a short deletion and has different key residues responsible for ACE2 binding. In addition, we showed that none of the known viruses in bat SARSr-CoV-2 lineage discovered uses human ACE2 as efficiently as the pangolin-derived SARSr-CoV-2 or some viruses in the SARSr-CoV-1 lineage. Therefore, further systematic and longitudinal studies in bats are needed to prevent future spillover events caused by SARSr-CoVs or to understand the origin of SARS-CoV-2 better.
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spelling doaj.art-4f4077eb64544fe7b8c355b7f237c4862022-12-21T19:29:10ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512021-01-011011507151410.1080/22221751.2021.1956373Identification of a novel lineage bat SARS-related coronaviruses that use bat ACE2 receptorHua Guo0Ben Hu1Hao-Rui Si2Yan Zhu3Wei Zhang4Bei Li5Ang Li6Rong Geng7Hao-Feng Lin8Xing-Lou Yang9Peng Zhou10Zheng-Li Shi11CAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan Institute of Virology, Wuhan, People’s Republic of ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan Institute of Virology, Wuhan, People’s Republic of ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan Institute of Virology, Wuhan, People’s Republic of ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan Institute of Virology, Wuhan, People’s Republic of ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan Institute of Virology, Wuhan, People’s Republic of ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan Institute of Virology, Wuhan, People’s Republic of ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan Institute of Virology, Wuhan, People’s Republic of ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan Institute of Virology, Wuhan, People’s Republic of ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan Institute of Virology, Wuhan, People’s Republic of ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan Institute of Virology, Wuhan, People’s Republic of ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan Institute of Virology, Wuhan, People’s Republic of ChinaCAS Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan Institute of Virology, Wuhan, People’s Republic of ChinaSevere respiratory disease coronavirus-2 (SARS-CoV-2) has been the most devastating disease COVID-19 in the century. One of the unsolved scientific questions of SARS-CoV-2 is the animal origin of this virus. Bats and pangolins are recognized as the most probable reservoir hosts that harbour highly similar SARS-CoV-2 related viruses (SARSr-CoV-2). This study identified 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 with SARS-CoV-2 in the conserved ORF1b region, it only shows less than 77.6% nucleotide identity to all known SARSr-CoVs at the genome level, thus forming a distinct lineage in the Sarbecovirus phylogenetic tree. We found that the RaTG15 receptor-binding domain (RBD) can bind to ACE2 from Rhinolophus affinis, Malayan pangolin, and use it as an entry receptor, except for ACE2 from humans. However, it contains a short deletion and has different key residues responsible for ACE2 binding. In addition, we showed that none of the known viruses in bat SARSr-CoV-2 lineage discovered uses human ACE2 as efficiently as the pangolin-derived SARSr-CoV-2 or some viruses in the SARSr-CoV-1 lineage. Therefore, further systematic and longitudinal studies in bats are needed to prevent future spillover events caused by SARSr-CoVs or to understand the origin of SARS-CoV-2 better.https://www.tandfonline.com/doi/10.1080/22221751.2021.1956373SARS-related coronavirusnovel lineagebatreservoir hostACE2
spellingShingle 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
Identification of a novel lineage bat SARS-related coronaviruses that use bat ACE2 receptor
Emerging Microbes and Infections
SARS-related coronavirus
novel lineage
bat
reservoir host
ACE2
title Identification of a novel lineage bat SARS-related coronaviruses that use bat ACE2 receptor
title_full Identification of a novel lineage bat SARS-related coronaviruses that use bat ACE2 receptor
title_fullStr Identification of a novel lineage bat SARS-related coronaviruses that use bat ACE2 receptor
title_full_unstemmed Identification of a novel lineage bat SARS-related coronaviruses that use bat ACE2 receptor
title_short Identification of a novel lineage bat SARS-related coronaviruses that use bat ACE2 receptor
title_sort identification of a novel lineage bat sars related coronaviruses that use bat ace2 receptor
topic SARS-related coronavirus
novel lineage
bat
reservoir host
ACE2
url https://www.tandfonline.com/doi/10.1080/22221751.2021.1956373
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