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

• Published in: Cell reports (Cambridge) Vol. 39; no. 7; p. 110812
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17.05.2022; The Authors; Elsevier
• Subjects: Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antibodies, Neutralizing - chemistry; Antibodies, Neutralizing - pharmacology; Antibodies, Neutralizing - therapeutic use; Antibodies, Viral; COVID-19; COVID-19 Drug Treatment; CP: Microbiology; Epitopes; Humans; neutralizing antibody; SARS-CoV-2; variant of concern; COVID-19; neutralizing antibody; variant of concern; SARS-CoV-2; CP: Microbiology
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.110812

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. [Display omitted] •LY-CoV1404 potently neutralizes SARS-CoV-2 Omicron, BA.2 Omicron, and Delta variants•No loss of potency against currently circulating variants•Binding epitope on RBD of SARS-CoV-2 is rarely mutated based on current GISAID data•Breadth of neutralizing activity and potency supports clinical development Westendorf et al. show that LY-CoV1404 is a potent SARS-CoV-2-binding antibody that neutralizes all known variants of concern and that its epitope is rarely mutated.