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Structure paper

TitleStructural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement.
Journal, issue, pagesScience, Vol. 375, Issue 6583, Page 864-868, Year 2022
Publish dateFeb 25, 2022
AuthorsMatthew 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 AbstractThe 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 linksScience / PubMed:35076256 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.85 - 3.3 Å
Structure data

EMDB-25990: SARS-CoV-2 S B.1.529 Omicron variant (RBD + S309 Local Refinement)
PDB-7tly: SARS-CoV-2 S B.1.1.529 Omicron variant (RBD + S309 Local Refinement)
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-25991, PDB-7tlz:
SARS-CoV-2 S NTD B.1.1.529 Omicron variant + S309 Local Refinement
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-25992, PDB-7tm0:
SARS-CoV-2 S B.1.1.529 Omicron variant + S309 + S2L20 Global Refinement
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-25993:
SARS-CoV-2 S B.1.1.529 Omicron variant + S309 + S2L20 Global Refinement (Two-open RBDs and one-closed RBD)
Method: EM (single particle) / Resolution: 3.2 Å

PDB-7tn0:
SARS-CoV-2 Omicron RBD in complex with human ACE2 and S304 Fab and S309 Fab
Method: X-RAY DIFFRACTION / Resolution: 2.85 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-EDO:
1,2-ETHANEDIOL

ChemComp-CL:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-HOH:
WATER

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRUS/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

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