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 GoyaMaia 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

Research output: Contribution to journalArticlepeer-review

188 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number110812
JournalCell Reports
Volume39
Issue number7
DOIs
StatePublished - May 17 2022

Keywords

  • COVID-19
  • CP: Microbiology
  • SARS-CoV-2
  • neutralizing antibody
  • variant of concern

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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