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Structural analysis of receptor engagement and antigenic drift within the BA.2 spike protein.
Saville, James W; Mannar, Dhiraj; Zhu, Xing; Berezuk, Alison M; Cholak, Spencer; Tuttle, Katharine S; Vahdatihassani, Faezeh; Subramaniam, Sriram.
  • Saville JW; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Mannar D; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Zhu X; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Berezuk AM; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Cholak S; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Tuttle KS; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Vahdatihassani F; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Subramaniam S; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Gandeeva Therapeutics, Inc., Burnaby, BC V5C 6N5, Canada. Electronic address: sriram.subramaniam@ubc.ca.
Cell Rep ; 42(1): 111964, 2023 01 31.
Article in English | MEDLINE | ID: covidwho-2165136
ABSTRACT
The BA.2 sub-lineage of the Omicron (B.1.1.529) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant rapidly supplanted the original BA.1 sub-lineage in early 2022. Both lineages threatened the efficacy of vaccine-elicited antibodies and acquired increased binding to several mammalian ACE2 receptors. Cryoelectron microscopy (cryo-EM) analysis of the BA.2 spike (S) glycoprotein in complex with mouse ACE2 (mACE2) identifies BA.1- and BA.2-mutated residues Q493R, N501Y, and Y505H as complementing non-conserved residues between human and mouse ACE2, rationalizing the enhanced S protein-mACE2 interaction for Omicron variants. Cryo-EM structures of the BA.2 S-human ACE2 complex and of the extensively mutated BA.2 amino-terminal domain (NTD) reveal a dramatic reorganization of the highly antigenic N1 loop into a ß-strand, providing an explanation for decreased binding of the BA.2 S protein to antibodies isolated from BA.1-convalescent patients. Our analysis reveals structural mechanisms underlying the antigenic drift in the rapidly evolving Omicron variant landscape.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 / Antigenic Drift and Shift Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: Cell Rep Year: 2023 Document Type: Article Affiliation country: J.celrep.2022.111964

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 / Antigenic Drift and Shift Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: Cell Rep Year: 2023 Document Type: Article Affiliation country: J.celrep.2022.111964