The Rhinolophus affinis bat ACE2 and multiple animal orthologs are functional receptors for bat coronavirus RaTG13 and SARS-CoV-2
Abstract Bat coronavirus (CoV) RaTG13 shares the highest genome sequence identity with SARS-CoV-2 among all known coronaviruses, and also uses human angiotensin converting enzyme 2 (hACE2) for virus entry. Thus, SARS-CoV-2 is thought to have originated from bat. However, whether SARS-CoV-2 emerged from bats directly or through an intermediate host remains elusive. Here, we found that Rhinolophus affinis bat ACE2 (RaACE2) is an entry receptor for both SARS-CoV-2 and RaTG13, although RaACE2 binding to the receptor binding domain (RBD) of SARS-CoV-2 is markedly weaker than that of hACE2. We further evaluated the receptor activities of ACE2s from additional 16 diverse animal species for RaTG13, SARS-CoV, and SARS-CoV-2 in terms of S protein binding, membrane fusion, and pseudovirus entry. We found that the RaTG13 spike (S) protein is significantly less fusogenic than SARS-CoV and SARS-CoV-2, and seven out of sixteen different ACE2s function as entry receptors for all three viruses, indicating that all three viruses might have broad host rages. Of note, RaTG13 S pseudovirions can use mouse, but not pangolin ACE2, for virus entry, whereas SARS-CoV-2 S pseudovirions can use pangolin, but limited for mouse, ACE2s enter cells. Mutagenesis analysis revealed that residues 484 and 498 in RaTG13 and SARS-CoV-2 S proteins play critical roles in recognition of mouse and human ACE2. Finally, two polymorphous Rhinolophous sinicus bat ACE2s showed different susceptibilities to virus entry by RaTG13 and SARS-CoV-2 S pseudovirions, suggesting possible coevolution. Our results offer better understanding of the mechanism of coronavirus entry, host range, and virus-host coevolution..
Medienart: |
Preprint |
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Erscheinungsjahr: |
2021 |
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Erschienen: |
2021 |
Enthalten in: |
bioRxiv.org - (2021) vom: 15. Dez. Zur Gesamtaufnahme - year:2021 |
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Sprache: |
Englisch |
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Beteiligte Personen: |
Li, Pei [VerfasserIn] |
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Links: |
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doi: |
10.1101/2020.11.16.385849 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
XBI019360495 |
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520 | |a Abstract Bat coronavirus (CoV) RaTG13 shares the highest genome sequence identity with SARS-CoV-2 among all known coronaviruses, and also uses human angiotensin converting enzyme 2 (hACE2) for virus entry. Thus, SARS-CoV-2 is thought to have originated from bat. However, whether SARS-CoV-2 emerged from bats directly or through an intermediate host remains elusive. Here, we found that Rhinolophus affinis bat ACE2 (RaACE2) is an entry receptor for both SARS-CoV-2 and RaTG13, although RaACE2 binding to the receptor binding domain (RBD) of SARS-CoV-2 is markedly weaker than that of hACE2. We further evaluated the receptor activities of ACE2s from additional 16 diverse animal species for RaTG13, SARS-CoV, and SARS-CoV-2 in terms of S protein binding, membrane fusion, and pseudovirus entry. We found that the RaTG13 spike (S) protein is significantly less fusogenic than SARS-CoV and SARS-CoV-2, and seven out of sixteen different ACE2s function as entry receptors for all three viruses, indicating that all three viruses might have broad host rages. Of note, RaTG13 S pseudovirions can use mouse, but not pangolin ACE2, for virus entry, whereas SARS-CoV-2 S pseudovirions can use pangolin, but limited for mouse, ACE2s enter cells. Mutagenesis analysis revealed that residues 484 and 498 in RaTG13 and SARS-CoV-2 S proteins play critical roles in recognition of mouse and human ACE2. Finally, two polymorphous Rhinolophous sinicus bat ACE2s showed different susceptibilities to virus entry by RaTG13 and SARS-CoV-2 S pseudovirions, suggesting possible coevolution. Our results offer better understanding of the mechanism of coronavirus entry, host range, and virus-host coevolution. | ||
700 | 1 | |a Guo, Ruixuan |e verfasserin |4 aut | |
700 | 1 | |a Liu, Yan |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Yintgtao |e verfasserin |4 aut | |
700 | 1 | |a Hu, Jiaxin |e verfasserin |4 aut | |
700 | 1 | |a Ou, Xiuyuan |e verfasserin |4 aut | |
700 | 1 | |a Mi, Dan |e verfasserin |4 aut | |
700 | 1 | |a Chen, Ting |e verfasserin |4 aut | |
700 | 1 | |a Mu, Zhixia |e verfasserin |4 aut | |
700 | 1 | |a Han, Yelin |e verfasserin |4 aut | |
700 | 1 | |a Cui, Zhewei |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Leiliang |e verfasserin |4 aut | |
700 | 1 | |a Wang, Xinquan |e verfasserin |4 aut | |
700 | 1 | |a Wu, Zhiqiang |e verfasserin |4 aut | |
700 | 1 | |a Wang, Jianwei |e verfasserin |4 aut | |
700 | 1 | |a Jin, Qi |e verfasserin |4 aut | |
700 | 1 | |a Qian, Zhaohui |e verfasserin |4 aut | |
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