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Mutations from bat ACE2 orthologs markedly enhance ACE2-Fc neutralization of SARS-CoV-2
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 Rhinoloph...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337384/ https://www.ncbi.nlm.nih.gov/pubmed/32637954 http://dx.doi.org/10.1101/2020.06.29.178459 |
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author | Mou, Huihui Quinlan, Brian D. Peng, Haiyong Guo, Yan Peng, Shoujiao Zhang, Lizhou Davis-Gardner, Meredith E. Gardner, Matthew R. Crynen, Gogce Voo, Zhi Xiang Bailey, Charles C. Alpert, Michael D. Rader, Christoph Choe, Hyeryun Farzan, Michael |
author_facet | Mou, Huihui Quinlan, Brian D. Peng, Haiyong Guo, Yan Peng, Shoujiao Zhang, Lizhou Davis-Gardner, Meredith E. Gardner, Matthew R. Crynen, Gogce Voo, Zhi Xiang Bailey, Charles C. Alpert, Michael D. Rader, Christoph Choe, Hyeryun Farzan, Michael |
author_sort | Mou, Huihui |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7337384 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-73373842020-07-07 Mutations from bat ACE2 orthologs markedly enhance ACE2-Fc neutralization of SARS-CoV-2 Mou, Huihui Quinlan, Brian D. Peng, Haiyong Guo, Yan Peng, Shoujiao Zhang, Lizhou Davis-Gardner, Meredith E. Gardner, Matthew R. Crynen, Gogce Voo, Zhi Xiang Bailey, Charles C. Alpert, Michael D. Rader, Christoph Choe, Hyeryun Farzan, Michael bioRxiv Article 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. Cold Spring Harbor Laboratory 2020-06-30 /pmc/articles/PMC7337384/ /pubmed/32637954 http://dx.doi.org/10.1101/2020.06.29.178459 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/It is made available under a CC-BY-NC-ND 4.0 International license (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Article Mou, Huihui Quinlan, Brian D. Peng, Haiyong Guo, Yan Peng, Shoujiao Zhang, Lizhou Davis-Gardner, Meredith E. Gardner, Matthew R. Crynen, Gogce Voo, Zhi Xiang Bailey, Charles C. Alpert, Michael D. Rader, Christoph Choe, Hyeryun Farzan, Michael Mutations from bat ACE2 orthologs markedly enhance ACE2-Fc neutralization of SARS-CoV-2 |
title | Mutations from bat ACE2 orthologs markedly enhance ACE2-Fc neutralization of SARS-CoV-2 |
title_full | Mutations from bat ACE2 orthologs markedly enhance ACE2-Fc neutralization of SARS-CoV-2 |
title_fullStr | Mutations from bat ACE2 orthologs markedly enhance ACE2-Fc neutralization of SARS-CoV-2 |
title_full_unstemmed | Mutations from bat ACE2 orthologs markedly enhance ACE2-Fc neutralization of SARS-CoV-2 |
title_short | Mutations from bat ACE2 orthologs markedly enhance ACE2-Fc neutralization of SARS-CoV-2 |
title_sort | mutations from bat ace2 orthologs markedly enhance ace2-fc neutralization of sars-cov-2 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337384/ https://www.ncbi.nlm.nih.gov/pubmed/32637954 http://dx.doi.org/10.1101/2020.06.29.178459 |
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