Mutations from bat ACE2 orthologs markedly enhance ACE2-Fc neutralization of SARS-CoV-2
SUMMARY The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates infection of cells expressing angiotensin-converting enzyme 2 (ACE2). ACE2 is also the viral receptor of SARS-CoV (SARS-CoV-1), a related coronavirus that emerged in 2002-2003. Horseshoe bats (genus Rhinolophus) are presumed to be the original reservoir of both viruses, and a SARS-like coronavirus, RaTG13, closely related SARS-CoV-2, has been isolated from one horseshoe-bat species. Here we characterize the ability of S-protein receptor-binding domains (RBDs) of SARS-CoV-1, SARS-CoV-2, and RaTG13 to bind a range of ACE2 orthologs. We observed that the SARS-CoV-2 RBD bound human, pangolin, and horseshoe bat (R. macrotis) ACE2 more efficiently than the SARS-CoV-1 or RaTG13 RBD. Only the RaTG13 RBD bound rodent ACE2 orthologs efficiently. Five mutations drawn from ACE2 orthologs of nine Rhinolophus species enhanced human ACE2 binding to the SARS-CoV-2 RBD and neutralization of SARS-CoV-2 by an immunoadhesin form of human ACE2 (ACE2-Fc). Two of these mutations impaired neutralization of SARS-CoV-1. An ACE2-Fc variant bearing all five mutations neutralized SARS-CoV-2 five-fold more efficiently than human ACE2-Fc. These data narrow the potential SARS-CoV-2 reservoir, suggest that SARS-CoV-1 and -2 originate from distinct bat species, and identify a more potently neutralizing form of ACE2-Fc..
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Preprint| 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: |
Mou, Huihui [VerfasserIn] |
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| Links: |
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| doi: |
10.1101/2020.06.29.178459 |
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| PPN (Katalog-ID): |
XBI018276849 |
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| 245 | 1 | 0 | |a Mutations from bat ACE2 orthologs markedly enhance ACE2-Fc neutralization of SARS-CoV-2 |
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| 520 | |a SUMMARY The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates infection of cells expressing angiotensin-converting enzyme 2 (ACE2). ACE2 is also the viral receptor of SARS-CoV (SARS-CoV-1), a related coronavirus that emerged in 2002-2003. Horseshoe bats (genus Rhinolophus) are presumed to be the original reservoir of both viruses, and a SARS-like coronavirus, RaTG13, closely related SARS-CoV-2, has been isolated from one horseshoe-bat species. Here we characterize the ability of S-protein receptor-binding domains (RBDs) of SARS-CoV-1, SARS-CoV-2, and RaTG13 to bind a range of ACE2 orthologs. We observed that the SARS-CoV-2 RBD bound human, pangolin, and horseshoe bat (R. macrotis) ACE2 more efficiently than the SARS-CoV-1 or RaTG13 RBD. Only the RaTG13 RBD bound rodent ACE2 orthologs efficiently. Five mutations drawn from ACE2 orthologs of nine Rhinolophus species enhanced human ACE2 binding to the SARS-CoV-2 RBD and neutralization of SARS-CoV-2 by an immunoadhesin form of human ACE2 (ACE2-Fc). Two of these mutations impaired neutralization of SARS-CoV-1. An ACE2-Fc variant bearing all five mutations neutralized SARS-CoV-2 five-fold more efficiently than human ACE2-Fc. These data narrow the potential SARS-CoV-2 reservoir, suggest that SARS-CoV-1 and -2 originate from distinct bat species, and identify a more potently neutralizing form of ACE2-Fc. | ||
| 700 | 1 | |a Quinlan, Brian D. |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Haiyong |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Shoujiao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Lizhou |e verfasserin |4 aut | |
| 700 | 1 | |a Davis-Gardner, Meredith E. |e verfasserin |4 aut | |
| 700 | 1 | |a Gardner, Matthew R. |e verfasserin |4 aut | |
| 700 | 1 | |a Crynen, Gogce |e verfasserin |4 aut | |
| 700 | 1 | |a Voo, Zhi Xiang |e verfasserin |4 aut | |
| 700 | 1 | |a Bailey, Charles C. |e verfasserin |4 aut | |
| 700 | 1 | |a Alpert, Michael D. |e verfasserin |4 aut | |
| 700 | 1 | |a Rader, Christoph |e verfasserin |4 aut | |
| 700 | 1 | |a Choe, Hyeryun |e verfasserin |4 aut | |
| 700 | 1 | |a Farzan, Michael |e verfasserin |4 aut | |
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