TY - JOUR T1 - LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants JF - bioRxiv DO - 10.1101/2021.04.30.442182 SP - 2021.04.30.442182 AU - Kathryn Westendorf AU - Lingshu Wang AU - Stefanie Žentelis AU - Denisa Foster AU - Peter Vaillancourt AU - Matthew Wiggin AU - Erica Lovett AU - Robin van der Lee AU - Jörg Hendle AU - Anna Pustilnik AU - J. Michael Sauder AU - Lucas Kraft AU - Yuri Hwang AU - Robert W. Siegel AU - Jinbiao Chen AU - Beverly A. Heinz AU - Richard E. Higgs AU - Nicole Kallewaard AU - Kevin Jepson AU - Rodrigo Goya AU - Maia A. Smith AU - David W. Collins AU - Davide Pellacani AU - Ping Xiang AU - Valentine de Puyraimond AU - Marketa Ricicova AU - Lindsay Devorkin AU - Caitlin Pritchard AU - Aoise O’Neill AU - Kush Dalal AU - Pankaj Panwar AU - Harveer Dhupar AU - Fabian A. Garces AU - Courtney Cohen AU - John Dye AU - Kathleen E. Huie AU - Catherine V. Badger AU - Darwyn Kobasa AU - Jonathan Audet AU - Joshua J. Freitas AU - Saleema Hassanali AU - Ina Hughes AU - Luis Munoz AU - Holly C. Palma AU - Bharathi Ramamurthy AU - Robert W. Cross AU - Thomas W. Geisbert AU - Vineet Menacherry AU - Kumari Lokugamage AU - Viktoriya Borisevich AU - Iliana Lanz AU - Lisa Anderson AU - Payal Sipahimalani AU - Kizzmekia S. Corbett AU - Eun Sung Yang AU - Yi Zhang AU - Wei Shi AU - Tongqing Zhou AU - Misook Choe AU - John Misasi AU - Peter D. Kwong AU - Nancy J. Sullivan AU - Barney S. Graham AU - Tara L. Fernandez AU - Carl L. Hansen AU - Ester Falconer AU - John R. Mascola AU - Bryan E. Jones AU - Bryan C. Barnhart Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/01/07/2021.04.30.442182.abstract N2 - 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, and B.1.1.529, and retains binding to spike proteins with a variety of underlying RBD mutations including K417N, L452R, E484K, and N501Y. Structural analysis demonstrates that RBD residues comprising 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.HighlightsLY-CoV1404 potently neutralizes SARS-CoV-2 authentic virus and known variants of concern including the B.1.1.529 (Omicron) 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 developmentCompeting Interest StatementD.F., P. V., A.P., J.H., J.M.S., R.W.S, J.C., I. H., J. J. F., S. H., H. C. P., B. R., B. A. H., R. W. S., J. C., J. M. S., R. E. H., N. K., and B.E.J. are employees and/or stockholders of Eli Lilly and Company. K.W., S. Z., M.W., E.L., L.K., Y.H., K.J., R.G., M.A.S., D.W.C., D.P., P.X., V.d.P., R.v.d.L., M.R., L.D., C.P., I.L., L.A., P.S., T.L.F., C.L.H, E.F., and B.C.B are employees and stockholders of AbCellera Biologics Inc. AbCellera Biologics Inc. and National Institutes of Health have filed patent applications related to the work described herein (US Patent Application No. 17/192243 and International Patent Application No. PCT/US21/20843, both titled: Anti-Coronavirus Antibodies and Methods of Use). ER -