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

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dc.creatorHanke, Leo
dc.creatorPerez, Laura Vidakovics
dc.creatorSheward, Daniel
dc.creatorDas, Hrishikesh
dc.creatorSchulte, Tim
dc.creatorMoliner-Morro, Ainhoa
dc.creatorCorcoran, Martin
dc.creatorAchour, Adnane
dc.creatorHedestam, Gunilla
dc.creatorHällberg, B Martin
dc.creatorMurrell, Ben
dc.creatorMcInerney, Gerald
dc.date.accessioned2020-09-18T03:26:26Z
dc.date.available2020-09-18T03:26:26Z
dc.date.created2020-09-04
dc.description.abstractenglishSARS-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.spa
dc.format.extent9 páginasspa
dc.format.mimetypeapplication/pdfspa
dc.identifier.doihttps://doi.org/10.1038/s41467-020-18174-5spa
dc.identifier.issn2041-1723spa
dc.identifier.otherhttps://www.nature.com/articles/s41467-020-18174-5spa
dc.identifier.urihttps://hdl.handle.net/20.500.12010/13442
dc.language.isoengspa
dc.publisherNature Communicationsspa
dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.rights.localAbierto (Texto Completo)spa
dc.sourcereponame:Expeditio Repositorio Institucional UJTLspa
dc.sourceinstname:Universidad de Bogotá Jorge Tadeo Lozanospa
dc.subjectSARS-CoV-2spa
dc.subject.lembSíndrome respiratorio agudo gravespa
dc.subject.lembCOVID-19spa
dc.subject.lembSARS-CoV-2spa
dc.subject.lembCoronavirusspa
dc.titleAn alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interactionspa
dc.type.coarhttp://purl.org/coar/resource_type/c_6501spa
dc.type.hasversioninfo:eu-repo/semantics/acceptedVersionspa
dc.type.localArtículospa

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