An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction

SARS-CoV-2 enters host cells through an interaction between the spike glycoprotein and the angiotensin converting enzyme 2 (ACE2) receptor. Directly preventing this interaction presents an attractive possibility for suppressing SARS-CoV-2 replication. Here, we report the isolation and characterizati...

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Autores:
Tipo de recurso:
Article of journal
Fecha de publicación:
2020
Institución:
Universidad de Bogotá Jorge Tadeo Lozano
Repositorio:
Expeditio: repositorio UTadeo
Idioma:
eng
OAI Identifier:
oai:expeditiorepositorio.utadeo.edu.co:20.500.12010/13442
Acceso en línea:
https://www.nature.com/articles/s41467-020-18174-5
http://hdl.handle.net/20.500.12010/13442
https://doi.org/10.1038/s41467-020-18174-5
Palabra clave:
SARS-CoV-2
Síndrome respiratorio agudo grave
COVID-19
SARS-CoV-2
Coronavirus
Rights
License
Abierto (Texto Completo)
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network_name_str Expeditio: repositorio UTadeo
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dc.title.spa.fl_str_mv An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction
title An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction
spellingShingle An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction
SARS-CoV-2
Síndrome respiratorio agudo grave
COVID-19
SARS-CoV-2
Coronavirus
title_short An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction
title_full An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction
title_fullStr An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction
title_full_unstemmed An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction
title_sort An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction
dc.subject.spa.fl_str_mv SARS-CoV-2
topic SARS-CoV-2
Síndrome respiratorio agudo grave
COVID-19
SARS-CoV-2
Coronavirus
dc.subject.lemb.spa.fl_str_mv Síndrome respiratorio agudo grave
COVID-19
SARS-CoV-2
Coronavirus
description SARS-CoV-2 enters host cells through an interaction between the spike glycoprotein and the angiotensin converting enzyme 2 (ACE2) receptor. Directly preventing this interaction presents an attractive possibility for suppressing SARS-CoV-2 replication. Here, we report the isolation and characterization of an alpaca-derived single domain antibody fragment, Ty1, that specifically targets the receptor binding domain (RBD) of the SARS-CoV-2 spike, directly preventing ACE2 engagement. Ty1 binds the RBD with high affinity, occluding ACE2. A cryo-electron microscopy structure of the bound complex at 2.9 Å resolution reveals that Ty1 binds to an epitope on the RBD accessible in both the ‘up’ and ‘down’ conformations, sterically hindering RBD-ACE2 binding. While fusion to an Fc domain renders Ty1 extremely potent, Ty1 neutralizes SARS-CoV-2 spike pseudovirus as a 12.8 kDa nanobody, which can be expressed in high quantities in bacteria, presenting opportunities for manufacturing at scale. Ty1 is therefore an excellent candidate as an intervention against COVID-19.
publishDate 2020
dc.date.accessioned.none.fl_str_mv 2020-09-18T03:26:26Z
dc.date.available.none.fl_str_mv 2020-09-18T03:26:26Z
dc.date.created.none.fl_str_mv 2020-09-04
dc.type.local.spa.fl_str_mv Artículo
dc.type.coar.spa.fl_str_mv http://purl.org/coar/resource_type/c_6501
format http://purl.org/coar/resource_type/c_6501
dc.identifier.issn.spa.fl_str_mv 2041-1723
dc.identifier.other.spa.fl_str_mv https://www.nature.com/articles/s41467-020-18174-5
dc.identifier.uri.none.fl_str_mv http://hdl.handle.net/20.500.12010/13442
dc.identifier.doi.spa.fl_str_mv https://doi.org/10.1038/s41467-020-18174-5
identifier_str_mv 2041-1723
url https://www.nature.com/articles/s41467-020-18174-5
http://hdl.handle.net/20.500.12010/13442
https://doi.org/10.1038/s41467-020-18174-5
dc.language.iso.spa.fl_str_mv eng
language eng
dc.rights.coar.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.rights.local.spa.fl_str_mv Abierto (Texto Completo)
rights_invalid_str_mv Abierto (Texto Completo)
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dc.format.extent.spa.fl_str_mv 9 páginas
dc.format.mimetype.spa.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv Nature Communications
dc.source.spa.fl_str_mv reponame:Expeditio Repositorio Institucional UJTL
instname:Universidad de Bogotá Jorge Tadeo Lozano
instname_str Universidad de Bogotá Jorge Tadeo Lozano
institution Universidad de Bogotá Jorge Tadeo Lozano
reponame_str Expeditio Repositorio Institucional UJTL
collection Expeditio Repositorio Institucional UJTL
bitstream.url.fl_str_mv https://expeditiorepositorio.utadeo.edu.co/bitstream/20.500.12010/13442/1/s41467-020-18174-5.pdf
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spelling 2020-09-18T03:26:26Z2020-09-18T03:26:26Z2020-09-042041-1723https://www.nature.com/articles/s41467-020-18174-5http://hdl.handle.net/20.500.12010/13442https://doi.org/10.1038/s41467-020-18174-59 páginasapplication/pdfengNature Communicationsreponame:Expeditio Repositorio Institucional UJTLinstname:Universidad de Bogotá Jorge Tadeo LozanoSARS-CoV-2Síndrome respiratorio agudo graveCOVID-19SARS-CoV-2CoronavirusAn alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interactionArtículohttp://purl.org/coar/resource_type/c_6501Abierto (Texto Completo)http://purl.org/coar/access_right/c_abf2SARS-CoV-2 enters host cells through an interaction between the spike glycoprotein and the angiotensin converting enzyme 2 (ACE2) receptor. Directly preventing this interaction presents an attractive possibility for suppressing SARS-CoV-2 replication. Here, we report the isolation and characterization of an alpaca-derived single domain antibody fragment, Ty1, that specifically targets the receptor binding domain (RBD) of the SARS-CoV-2 spike, directly preventing ACE2 engagement. Ty1 binds the RBD with high affinity, occluding ACE2. A cryo-electron microscopy structure of the bound complex at 2.9 Å resolution reveals that Ty1 binds to an epitope on the RBD accessible in both the ‘up’ and ‘down’ conformations, sterically hindering RBD-ACE2 binding. While fusion to an Fc domain renders Ty1 extremely potent, Ty1 neutralizes SARS-CoV-2 spike pseudovirus as a 12.8 kDa nanobody, which can be expressed in high quantities in bacteria, presenting opportunities for manufacturing at scale. Ty1 is therefore an excellent candidate as an intervention against COVID-19.Hanke, LeoPerez, Laura VidakovicsSheward, DanielDas, HrishikeshSchulte, TimMoliner-Morro, AinhoaCorcoran, MartinAchour, AdnaneHedestam, GunillaHällberg, B MartinMurrell, BenMcInerney, GeraldORIGINALs41467-020-18174-5.pdfs41467-020-18174-5.pdfVer documentoapplication/pdf3174439https://expeditiorepositorio.utadeo.edu.co/bitstream/20.500.12010/13442/1/s41467-020-18174-5.pdf3b322d55abe485af496742fa54104e2dMD51open accessLICENSElicense.txtlicense.txttext/plain; charset=utf-82938https://expeditiorepositorio.utadeo.edu.co/bitstream/20.500.12010/13442/2/license.txtabceeb1c943c50d3343516f9dbfc110fMD52open accessTHUMBNAILs41467-020-18174-5.pdf.jpgs41467-020-18174-5.pdf.jpgIM Thumbnailimage/jpeg16463https://expeditiorepositorio.utadeo.edu.co/bitstream/20.500.12010/13442/3/s41467-020-18174-5.pdf.jpgc3325f1e13fa5d9640eb4037a977dcb1MD53open access20.500.12010/13442oai:expeditiorepositorio.utadeo.edu.co:20.500.12010/134422020-09-17 22:26:26.992open accessRepositorio Institucional - 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