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-Structure paper
Title | Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement. |
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Journal, issue, pages | Science, Vol. 375, Issue 6583, Page 864-868, Year 2022 |
Publish date | Feb 25, 2022 |
Authors | Matthew McCallum / Nadine Czudnochowski / Laura E Rosen / Samantha K Zepeda / John E Bowen / Alexandra C Walls / Kevin Hauser / Anshu Joshi / Cameron Stewart / Josh R Dillen / Abigail E Powell / Tristan I Croll / Jay Nix / Herbert W Virgin / Davide Corti / Gyorgy Snell / David Veesler / |
PubMed Abstract | The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern evades antibody-mediated immunity that comes from vaccination or infection with earlier variants due to ...The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern evades antibody-mediated immunity that comes from vaccination or infection with earlier variants due to accumulation of numerous spike mutations. To understand the Omicron antigenic shift, we determined cryo-electron microscopy and x-ray crystal structures of the spike protein and the receptor-binding domain bound to the broadly neutralizing sarbecovirus monoclonal antibody (mAb) S309 (the parent mAb of sotrovimab) and to the human ACE2 receptor. We provide a blueprint for understanding the marked reduction of binding of other therapeutic mAbs that leads to dampened neutralizing activity. Remodeling of interactions between the Omicron receptor-binding domain and human ACE2 likely explains the enhanced affinity for the host receptor relative to the ancestral virus. |
External links | Science / PubMed:35076256 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 2.85 - 3.3 Å |
Structure data | EMDB-25990: SARS-CoV-2 S B.1.529 Omicron variant (RBD + S309 Local Refinement) EMDB-25991, PDB-7tlz: EMDB-25992, PDB-7tm0: EMDB-25993: PDB-7tn0: |
Chemicals | ChemComp-NAG: ChemComp-EDO: ChemComp-CL: ChemComp-ZN: ChemComp-HOH: |
Source |
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Keywords | VIRUS/IMMUNE SYSTEM / omicron / receptor-binding domain / SARS-CoV-2 / covid / B.1.529 / RBD / antibody / Fab / S309 / sotrovimab / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / VIRUS-IMMUNE SYSTEM complex / NTD / S2L20 / VIRUS / VIRAL PROTEIN/IMMUNE SYSTEM / COVID-19 / neutralizing monoclonal antibody / SARS-CoV-2 receptor human ACE2 / VIRAL PROTEIN-IMMUNE SYSTEM complex |