TY - JOUR
T1 - A nanobody recognizes a unique conserved epitope and potently neutralizes SARS-CoV-2 omicron variants
T2 - A nanobody recognizes a unique conserved epitope and potently neutralizes against the SARS-CoV-2 omicron variants
AU - Modhiran, Naphak
AU - Lauer, Simon Malte
AU - Amarilla, Alberto A
AU - Hewins, Peter
AU - Lopes van den Broek, Sara Irene
AU - Low, Yu Shang
AU - Thakur, Nazia
AU - Liang, Benjamin
AU - Nieto, Guillermo Valenzuela
AU - Jung, James
AU - Paramitha, Devina
AU - Isaacs, Ariel
AU - Sng, Julian D J
AU - Song, David
AU - Jørgensen, Jesper Tranekjær
AU - Cheuquemilla, Yorka
AU - Bürger, Jörg
AU - Andersen, Ida Vang
AU - Himelreichs, Johanna
AU - Jara, Ronald
AU - MacLoughlin, Ronan
AU - Miranda-Chacon, Zaray
AU - Chana-Cuevas, Pedro
AU - Kramer, Vasko
AU - Spahn, Christian M T
AU - Mielke, Thorsten
AU - Khromykh, Alexander A
AU - Munro, Trent
AU - Jones, Martina L
AU - Young, Paul R
AU - Chappell, Keith
AU - Bailey, Dalan
AU - Kjaer, Andreas
AU - Herth, Matthias Manfred
AU - Jurado, Kellie Ann
AU - Schwefel, David
AU - Rojas-Fernandez, Alejandro
AU - Watterson, Daniel
N1 - © 2023.
PY - 2023/7/21
Y1 - 2023/7/21
N2 - 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 properties. Together, these data endorse W25 for further clinical development.
AB - 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 properties. Together, these data endorse W25 for further clinical development.
KW - Decision science
KW - Information system model
KW - Public health
UR - https://www.scopus.com/pages/publications/85163012283
U2 - 10.1016/j.isci.2023.107085
DO - 10.1016/j.isci.2023.107085
M3 - Journal article
C2 - 37361875
SN - 2589-0042
VL - 26
SP - 1
EP - 26
JO - iScience
JF - iScience
IS - 7
M1 - 107085
ER -