| Autor: |
Naphak Modhiran, Simon Malte Lauer, Alberto A Amarilla, Peter Hewins, Sara Irene Lopes van den Broek, Yu Shang Low, Nazia Thakur, Benjamin Liang, Guillermo Valenzuela Nieto, James Jung, Devina Paramitha, Ariel Isaacs, Julian de Sng, David Song, Jesper Tranekjær Jørgensen, Yorka Cheuquemilla, Jörg Bürger, Ida Vang Andersen, Johanna Himelreichs, Ronald Jara, Ronan MacLoughlin, Zaray Miranda-Chacon, Pedro Chana-Cuevas, Vasko Kramer, Christian M.T. Spahn, Thorsten Mielke, Alexander A Khromykh, Trent Munro, Martina Jones, Paul R Young, Keith Chappell, Dalan Bailey, Andreas Kjaer, Matthias Manfred Herth, Kellie Ann Jurado, David Schwefel, Alejandro Rojas-Fernandez, Daniel Watterson |
| Rok vydání: |
2022 |
| Popis: |
The SARS-CoV2 Omicron variant sub-lineages spread rapidly through the world, 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 anti-SARS-CoV-2 agents that are effective 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 RBD-specific nanobody W25, which we previously isolated from an alpaca, and show superior neutralization activity towards Omicron lineage BA.1 in comparison to all other SARS-CoV2 variants. Structure analysis of W25 in complex with the SARS-CoV2 spike surface glycoprotein shows that W25 engages an RBD epitope not covered by any of the antibodies previously approved for emergency use. Furthermore, we show that W25 also binds the spike protein from the emerging, more infectious Omicron BA.2 lineage with picomolar affinity.In vivoevaluation 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 properties. Together, these data endorse prioritization of W25 for further clinical development. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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