A nanobody recognizes a unique conserved epitope and neutralizes SARS-CoV-2 omicron variants

Modhiran, Naphak; Lauer, Simon Malte; Amarilla, Alberto A.; Hewins, Peter; Broek, Sara Irene Lopes van den; Low, Yu Shang; Thakur, Nazia; Liang, Benjamin; Nieto, Guillermo Valenzuela; Jung, James; Paramitha, Devina; Isaacs, Ariel; Sng, Julian D. J.; Song, David; Jorgensen, Jesper Tranekjaer; et. al.


The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) Omicron variant sub-lineages spread rapidly worldwide, mostly due to their immune-evasive properties. This has put a significant part of the population at risk for severe disease and underscores the need for effective anti-SARS-CoV-2 agents against emergent strains in vulnerable patients. Camelid nanobodies are attractive therapeutic candidates due to their high stability, ease of large-scale production, and potential for delivery via inhalation. Here, we characterize the receptor binding domain (RBD)-specific nanobody W25 and show superior neutralization activity toward Omicron sub-lineages in comparison to all other SARS-CoV2 variants. Structure analysis of W25 in complex with the SARS-CoV2 spike glycoprotein shows that W25 engages an RBD epitope not covered by any of the antibodies previously approved for emergency use. In vivo evaluation of W25 prophylactic and therapeutic treatments across multiple SARS-CoV-2 variant infection models, together with W25 biodistribution analysis in mice, demonstrates favorable pre-clinical proper-ties. Together, these data endorse W25 for further clinical development.

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Título según WOS: ID WOS:001056899500001 Not found in local WOS DB
Título de la Revista: ISCIENCE
Volumen: 26
Número: 7
Editorial: Cell Press
Fecha de publicación: 2023


Notas: ISI