Authors: Westendorf K, Zentelis S, Wang L, Foster D, Wiggin M, Lovett E
PMID: 33972947 PMCID: PMC8109210 DOI: 10.1101/2021.04.30.442182
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bioRxiv
. 2022 Mar 24:2021.04.30.442182. doi: 10.1101/2021.04.30.442182. Preprint
LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants
Kathryn Westendorf, Stefanie Žentelis, Lingshu Wang, Denisa Foster, Peter Vaillancourt, Matthew Wiggin, Erica Lovett, Robin van der Lee, Jörg Hendle, Anna Pustilnik, J Michael Sauder, Lucas Kraft, Yuri Hwang, Robert W Siegel, Jinbiao Chen, Beverly A Heinz, Richard E Higgs, Nicole L Kallewaard, Kevin Jepson, Rodrigo Goya, Maia A Smith, David W Collins, Davide Pellacani, Ping Xiang, Valentine de Puyraimond, Marketa Ricicova, Lindsay Devorkin, Caitlin Pritchard, Aoise O’Neill, Kush Dalal, Pankaj Panwar, Harveer Dhupar, Fabian A Garces, Courtney A Cohen, John M Dye, Kathleen E Huie, Catherine V Badger, Darwyn Kobasa, Jonathan Audet, Joshua J Freitas, Saleema Hassanali, Ina Hughes, Luis Munoz, Holly C Palma, Bharathi Ramamurthy, Robert W Cross, Thomas W Geisbert, Vineet Menacherry, Kumari Lokugamage, Viktoriya Borisevich, Iliana Lanz, Lisa Anderson, Payal Sipahimalani, Kizzmekia S Corbett, Eun Sung Yang, Yi Zhang, Wei Shi, Tongqing Zhou, Misook Choe, John Misasi, Peter D Kwong, Nancy J Sullivan, Barney S Graham, Tara L Fernandez, Carl L Hansen, Ester Falconer, John R Mascola, Bryan E Jones, Bryan C Barnhart
PMID: 33972947 PMCID: PMC8109210 DOI: 10.1101/2021.04.30.442182
Free PMC article
Update in
LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants.
Westendorf K, Žentelis S, Wang L, Foster D, Vaillancourt P, Wiggin M, Lovett E, van der Lee R, Hendle J, Pustilnik A, Sauder JM, Kraft L, Hwang Y, Siegel RW, Chen J, Heinz BA, Higgs RE, Kallewaard NL, Jepson K, Goya R, Smith MA, Collins DW, Pellacani D, Xiang P, de Puyraimond V, Ricicova M, Devorkin L, Pritchard C, O’Neill A, Dalal K, Panwar P, Dhupar H, Garces FA, Cohen CA, Dye JM, Huie KE, Badger CV, Kobasa D, Audet J, Freitas JJ, Hassanali S, Hughes I, Munoz L, Palma HC, Ramamurthy B, Cross RW, Geisbert TW, Menachery V, Lokugamage K, Borisevich V, Lanz I, Anderson L, Sipahimalani P, Corbett KS, Yang ES, Zhang Y, Shi W, Zhou T, Choe M, Misasi J, Kwong PD, Sullivan NJ, Graham BS, Fernandez TL, Hansen CL, Falconer E, Mascola JR, Jones BE, Barnhart BC.
Cell Rep. 2022 May 17;39(7):110812. doi: 10.1016/j.celrep.2022.110812. Epub 2022 Apr 25.
PMID: 35568025 Free PMC article.
Abstract
SARS-CoV-2 neutralizing monoclonal antibodies (mAbs) can reduce the risk of hospitalization when administered early during COVID-19 disease. However, the emergence of variants of concern has negatively impacted the therapeutic use of some authorized mAbs. Using a high throughput B-cell screening pipeline, we isolated a highly potent SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody called LY-CoV1404 (also known as bebtelovimab). LY-CoV1404 potently neutralizes authentic SARS-CoV-2 virus, including the prototype, B.1.1.7, B.1.351 and B.1.617.2). In pseudovirus neutralization studies, LY-CoV1404 retains potent neutralizing activity against numerous 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 and retains binding to spike proteins with a variety of underlying RBD mutations including K417N, L452R, E484K, and N501Y. Structural analysis reveals that the contact residues of the LY-CoV1404 epitope are highly conserved with the exception of N439 and N501. Notably, the binding and neutralizing activity of LY-CoV1404 is unaffected by the most common mutations at these positions (N439K and N501Y). The breadth of reactivity to amino acid substitutions present among current VOC together with broad and potent neutralizing activity and the relatively conserved epitope suggest that LY-CoV1404 has the potential to be an effective therapeutic agent to treat all known variants causing COVID-19.
In brief: LY-CoV1404 is a potent SARS-CoV-2-binding antibody that neutralizes all known variants of concern and whose epitope is rarely mutated.
Highlights: LY-CoV1404 potently neutralizes SARS-CoV-2 authentic virus and known variants of concern including the B.1.1.529 (Omicron), the BA.2 Omicron subvariant, and B.1.617.2 (Delta) variantsNo loss of potency against currently circulating variantsBinding epitope on RBD of SARS-CoV-2 is rarely mutated in GISAID databaseBreadth of neutralizing activity and potency supports clinical development.
Keywords: bebtelovimab, SARS-CoV-2
Source: https://pubmed.ncbi.nlm.nih.gov/33972947/
Archive: https://archive.ph/ME2B9
