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LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants.
Westendorf, Kathryn; Zentelis, Stefanie; Wang, Lingshu; Foster, Denisa; Vaillancourt, Peter; Wiggin, Matthew; Lovett, Erica; van der Lee, Robin; Hendle, Jörg; Pustilnik, Anna; Sauder, J Michael; Kraft, Lucas; Hwang, Yuri; Siegel, Robert W; Chen, Jinbiao; Heinz, Beverly A; Higgs, Richard E; Kallewaard, Nicole L; Jepson, Kevin; Goya, Rodrigo; Smith, Maia A; Collins, David W; Pellacani, Davide; Xiang, Ping; de Puyraimond, Valentine; Ricicova, Marketa; Devorkin, Lindsay; Pritchard, Caitlin; O'Neill, Aoise; Dalal, Kush; Panwar, Pankaj; Dhupar, Harveer; Garces, Fabian A; Cohen, Courtney A; Dye, John M; Huie, Kathleen E; Badger, Catherine V; Kobasa, Darwyn; Audet, Jonathan; Freitas, Joshua J; Hassanali, Saleema; Hughes, Ina; Munoz, Luis; Palma, Holly C; Ramamurthy, Bharathi; Cross, Robert W; Geisbert, Thomas W; Menachery, Vineet; Lokugamage, Kumari; Borisevich, Viktoriya.
  • Westendorf K; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada.
  • Zentelis S; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada.
  • Wang L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Foster D; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA.
  • Vaillancourt P; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA.
  • Wiggin M; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada.
  • Lovett E; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada.
  • van der Lee R; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada.
  • Hendle J; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA.
  • Pustilnik A; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA.
  • Sauder JM; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA.
  • Kraft L; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada.
  • Hwang Y; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada.
  • Siegel RW; Eli Lilly and Company, Indianapolis, IN 46285, USA.
  • Chen J; Eli Lilly and Company, Indianapolis, IN 46285, USA.
  • Heinz BA; Eli Lilly and Company, Indianapolis, IN 46285, USA.
  • Higgs RE; Eli Lilly and Company, Indianapolis, IN 46285, USA.
  • Kallewaard NL; Eli Lilly and Company, Indianapolis, IN 46285, USA.
  • Jepson K; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada.
  • Goya R; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada.
  • Smith MA; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada.
  • Collins DW; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada.
  • Pellacani D; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada.
  • Xiang P; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada.
  • de Puyraimond V; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada.
  • Ricicova M; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada.
  • Devorkin L; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada.
  • Pritchard C; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada.
  • O'Neill A; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada.
  • Dalal K; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada.
  • Panwar P; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada.
  • Dhupar H; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada.
  • Garces FA; AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada.
  • Cohen CA; U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD 21702, USA.
  • Dye JM; U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD 21702, USA.
  • Huie KE; U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD 21702, USA.
  • Badger CV; U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD 21702, USA.
  • Kobasa D; National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3L5, Canada; University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
  • Audet J; National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3L5, Canada; University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
  • Freitas JJ; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA.
  • Hassanali S; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA.
  • Hughes I; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA.
  • Munoz L; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA.
  • Palma HC; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA.
  • Ramamurthy B; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA.
  • Cross RW; University of Manitoba, Winnipeg, MB R3T 2N2, Canada; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Geisbert TW; University of Manitoba, Winnipeg, MB R3T 2N2, Canada; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Menachery V; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Lokugamage K; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Borisevich V; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Cell Rep ; 39(7): 110812, 2022 05 17.
Article in English | MEDLINE | ID: covidwho-1803708
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Prognostic study Topics: Variants Limits: Humans Language: English Journal: Cell Rep Year: 2022 Document Type: Article Affiliation country: J.celrep.2022.110812

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Prognostic study Topics: Variants Limits: Humans Language: English Journal: Cell Rep Year: 2022 Document Type: Article Affiliation country: J.celrep.2022.110812