LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants
2022
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
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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