Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement
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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 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.
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SciScore for 10.1101/2021.12.28.474380: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Particles in well-formed 3D classes were then used for local refinement in cryoSPARC. cryoSPARCsuggested: (cryoSPARC, RRID:SCR_016501)) and Coot (58) were used to fit atomic models of S2L20, S309, and SARS-CoV-2 S (PDB 7SOB) into the cryo-EM maps. Cootsuggested: (Coot, RRID:SCR_014222)Model validation and analysis used MolProbity (63), EMRinger (64), Phenix (61), and Privateer (65). MolProbitysuggested: (MolProbity, RRID:SCR_014226)Cell culture supernatant was collected eight days after transfection and supplemented to a final concentration of 80 mM Tris-HCl pH 8.0, 100 mM NaCl, and then … SciScore for 10.1101/2021.12.28.474380: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Particles in well-formed 3D classes were then used for local refinement in cryoSPARC. cryoSPARCsuggested: (cryoSPARC, RRID:SCR_016501)) and Coot (58) were used to fit atomic models of S2L20, S309, and SARS-CoV-2 S (PDB 7SOB) into the cryo-EM maps. Cootsuggested: (Coot, RRID:SCR_014222)Model validation and analysis used MolProbity (63), EMRinger (64), Phenix (61), and Privateer (65). MolProbitysuggested: (MolProbity, RRID:SCR_014226)Cell culture supernatant was collected eight days after transfection and supplemented to a final concentration of 80 mM Tris-HCl pH 8.0, 100 mM NaCl, and then incubated with BioLock (IBA GmbH) solution. hACE2 was purified using a 5 mL StrepTrap HP column (Cytiva) followed by size exclusion chromatography using a Superdex 200 Increase 10/300 GL column (Cytiva) pre-equilibrated in PBS. BioLocksuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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