dc.contributor.author
Rothenberger, Sylvia
dc.contributor.author
Hurdiss, Daniel L.
dc.contributor.author
Adler, Julia M.
dc.contributor.author
Eschke, Kathrin
dc.contributor.author
Nascimento, Mariana
dc.contributor.author
Abdelgawad, Azza
dc.contributor.author
Gruber, Achim D.
dc.contributor.author
Bushe, Judith
dc.contributor.author
Kershaw, Olivia
dc.contributor.author
Trimpert, Jakob
dc.date.accessioned
2023-01-02T10:29:21Z
dc.date.available
2023-01-02T10:29:21Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/36162
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-35878
dc.description.abstract
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with potential resistance to existing drugs emphasizes the need for new therapeutic modalities with broad variant activity. Here we show that ensovibep, a trispecific DARPin (designed ankyrin repeat protein) clinical candidate, can engage the three units of the spike protein trimer of SARS-CoV-2 and inhibit ACE2 binding with high potency, as revealed by cryo-electron microscopy analysis. The cooperative binding together with the complementarity of the three DARPin modules enable ensovibep to inhibit frequent SARS-CoV-2 variants, including Omicron sublineages BA.1 and BA.2. In Roborovski dwarf hamsters infected with SARS-CoV-2, ensovibep reduced fatality similarly to a standard-of-care monoclonal antibody (mAb) cocktail. When used as a single agent in viral passaging experiments in vitro, ensovibep reduced the emergence of escape mutations in a similar fashion to the same mAb cocktail. These results support further clinical evaluation of ensovibep as a broad variant alternative to existing targeted therapies for Coronavirus Disease 2019 (COVID-19).
en
dc.format.extent
20 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
Antiviral agents
en
dc.subject
Cryoelectron microscopy
en
dc.subject.ddc
500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie::570 Biowissenschaften; Biologie
dc.title
The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1038/s41587-022-01382-3
dcterms.bibliographicCitation.journaltitle
Nature Biotechnology
dcterms.bibliographicCitation.number
12
dcterms.bibliographicCitation.pagestart
1845
dcterms.bibliographicCitation.pageend
1854
dcterms.bibliographicCitation.volume
40
dcterms.bibliographicCitation.url
https://doi.org/10.1038/s41587-022-01382-3
refubium.affiliation
Veterinärmedizin
refubium.affiliation.other
Institut für Virologie
refubium.affiliation.other
Institut für Tierpathologie
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
1546-1696
refubium.resourceType.provider
WoS-Alert