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 Menachery; 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

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

2022

Summary: 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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