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About:
Mutations from bat ACE2 orthologs markedly enhance ACE2-Fc neutralization of SARS-CoV-2
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schema:ScholarlyArticle
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wasabi.inria.fr
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Type:
Academic Article
research paper
schema:ScholarlyArticle
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type
Academic Article
research paper
schema:ScholarlyArticle
isDefinedBy
Covid-on-the-Web dataset
has title
Mutations from bat ACE2 orthologs markedly enhance ACE2-Fc neutralization of SARS-CoV-2
Creator
Guo, Yan
Farzan, Michael
Choe, Hyeryun
Mou, Huihui
Bailey, Charles
Rader, Christoph
Zhang, Lizhou
Alpert, Michael
Crynen, Gogce
Davis-Gardner, Meredith
Gardner, Matthew
Peng, Haiyong
Peng, Shoujiao
Quinlan, Brian
Voo, Zhi
Source
BioRxiv; Medline; PMC
abstract
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.
has issue date
2020-06-30
(
xsd:dateTime
)
bibo:doi
10.1101/2020.06.29.178459
bibo:pmid
32637954
has license
cc-by-nc-nd
sha1sum (hex)
cf80a18de5e8b8099e1aef0f3f7af84e9aced5e4
schema:url
https://doi.org/10.1101/2020.06.29.178459
resource representing a document's title
Mutations from bat ACE2 orthologs markedly enhance ACE2-Fc neutralization of SARS-CoV-2
has PubMed Central identifier
PMC7337384
has PubMed identifier
32637954
schema:publication
bioRxiv
resource representing a document's body
covid:cf80a18de5e8b8099e1aef0f3f7af84e9aced5e4#body_text
is
schema:about
of
named entity 'SARS-CoV'
named entity 'SARS-CoV-2'
named entity 'SARS-CoV-2'
named entity 'SARS-CoV-2'
named entity 'ACE2'
named entity 'ACE2'
named entity 'binding'
named entity 'neutralization'
named entity 'SARS-CoV-2'
named entity 'orthologs'
named entity 'RBD'
named entity 'neutralizing'
named entity 'neutralization'
named entity 'enhanced'
named entity 'coronavirus'
named entity 'viruses'
named entity 'range'
named entity 'SARS-CoV-1'
named entity 'efficiently'
named entity 'SARS-like coronavirus'
named entity 'bound'
named entity 'genus'
named entity 'RBD'
named entity 'horseshoe bat'
named entity 'ACE2'
named entity 'bat species'
named entity 'ACE2'
named entity 'Horseshoe bats'
named entity 'horseshoe bats'
named entity 'RBD'
named entity 'SARS-CoV-2'
named entity 'SARS-CoV-1'
named entity 'viruses'
named entity 'SARS-CoV-2'
named entity 'orthologs'
named entity 'genus'
named entity 'ACE2'
named entity 'SARS-CoV-2'
named entity 'SARS-CoV-1'
named entity 'coronavirus'
named entity 'ACE2'
named entity 'Rhinolophus'
named entity 'SARS-CoV'
named entity 'orthologs'
named entity 'bound'
named entity 'bat'
named entity 'orthologs'
named entity 'viral membrane'
named entity 'serine'
named entity 'RBD'
named entity 'CC-BY-NC-ND 4.0'
named entity '293T'
named entity 'amino-acids'
named entity 'initial infection'
named entity 'receptor'
named entity 'virus'
named entity 'flow cytometry'
named entity 'pangolin'
named entity 'Wrapp'
named entity 'orthologs'
named entity 'incubation'
named entity 'SARS2'
named entity 'bat species'
named entity 'ACE2'
named entity 'pangolins'
named entity 'protein'
named entity 'IgG1'
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