LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing monoclonal antibodies (mAbs) can reduce the risk of hospitalization from coronavirus disease 2019 (COVID-19) when administered early. However, SARS-CoV-2 variants of concern (VOCs) have negatively affected therapeutic use of s...

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Detalles Bibliográficos
Autores principales: Westendorf, Kathryn, Žentelis, Stefanie, Wang, Lingshu, Foster, Denisa, Vaillancourt, Peter, Wiggin, Matthew, Lovett, Erica, van der Lee, Robin, Hendle, Jörg, Pustilnik, Anna, Sauder, J. Michael, Kraft, Lucas, Hwang, Yuri, Siegel, Robert W., Chen, Jinbiao, Heinz, Beverly A., Higgs, Richard E., Kallewaard, Nicole L., Jepson, Kevin, Goya, Rodrigo, Smith, Maia A., Collins, David W., Pellacani, Davide, Xiang, Ping, de Puyraimond, Valentine, Ricicova, Marketa, Devorkin, Lindsay, Pritchard, Caitlin, O’Neill, Aoise, Dalal, Kush, Panwar, Pankaj, Dhupar, Harveer, Garces, Fabian A., Cohen, Courtney A., Dye, John M., Huie, Kathleen E., Badger, Catherine V., Kobasa, Darwyn, Audet, Jonathan, Freitas, Joshua J., Hassanali, Saleema, Hughes, Ina, Munoz, Luis, Palma, Holly C., Ramamurthy, Bharathi, Cross, Robert W., Geisbert, Thomas W., Menachery, Vineet, Lokugamage, Kumari, Borisevich, Viktoriya, Lanz, Iliana, Anderson, Lisa, Sipahimalani, Payal, Corbett, Kizzmekia S., Yang, Eun Sung, Zhang, Yi, Shi, Wei, Zhou, Tongqing, Choe, Misook, Misasi, John, Kwong, Peter D., Sullivan, Nancy J., Graham, Barney S., Fernandez, Tara L., Hansen, Carl L., Falconer, Ester, Mascola, John R., Jones, Bryan E., Barnhart, Bryan C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Authors. 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035363/
https://www.ncbi.nlm.nih.gov/pubmed/35568025
http://dx.doi.org/10.1016/j.celrep.2022.110812
Descripción
Sumario:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing monoclonal antibodies (mAbs) can reduce the risk of hospitalization from coronavirus disease 2019 (COVID-19) when administered early. However, SARS-CoV-2 variants of concern (VOCs) have negatively affected therapeutic use of some authorized mAbs. Using a high-throughput B cell screening pipeline, we isolated LY-CoV1404 (bebtelovimab), a highly potent SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody. LY-CoV1404 potently neutralizes authentic SARS-CoV-2, B.1.1.7, B.1.351, and B.1.617.2. In pseudovirus neutralization studies, LY-CoV1404 potently neutralizes variants, including B.1.1.7, B.1.351, B.1.617.2, B.1.427/B.1.429, P.1, B.1.526, B.1.1.529, and the BA.2 subvariant. Structural analysis reveals that the contact residues of the LY-CoV1404 epitope are highly conserved, except for N439 and N501. The binding and neutralizing activity of LY-CoV1404 is unaffected by the most common mutations at these positions (N439K and N501Y). The broad and potent neutralization activity and the relatively conserved epitope suggest that LY-CoV1404 has the potential to be an effective therapeutic agent to treat all known variants.

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