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Title | SARS-CoV-2 variants of concern: spike protein mutational analysis and epitope for broad neutralization. |
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Journal, issue, pages | Nat Commun, Vol. 13, Issue 1, Page 4696, Year 2022 |
Publish date | Aug 18, 2022 |
Authors | Dhiraj Mannar / James W Saville / Zehua Sun / Xing Zhu / Michelle M Marti / Shanti S Srivastava / Alison M Berezuk / Steven Zhou / Katharine S Tuttle / Michele D Sobolewski / Andrew Kim / Benjamin R Treat / Priscila Mayrelle Da Silva Castanha / Jana L Jacobs / Simon M Barratt-Boyes / John W Mellors / Dimiter S Dimitrov / Wei Li / Sriram Subramaniam / |
PubMed Abstract | Mutations in the spike glycoproteins of SARS-CoV-2 variants of concern have independently been shown to enhance aspects of spike protein fitness. Here, we describe an antibody fragment (V ab6) that ...Mutations in the spike glycoproteins of SARS-CoV-2 variants of concern have independently been shown to enhance aspects of spike protein fitness. Here, we describe an antibody fragment (V ab6) that neutralizes all major variants including the recently emerged BA.1 and BA.2 Omicron subvariants, with a unique mode of binding revealed by cryo-EM studies. Further, we provide a comparative analysis of the mutational effects within previously emerged variant spikes and identify the structural role of mutations within the NTD and RBD in evading antibody neutralization. Our analysis shows that the highly mutated Gamma N-terminal domain exhibits considerable structural rearrangements, partially explaining its decreased neutralization by convalescent sera. Our results provide mechanistic insights into the structural, functional, and antigenic consequences of SARS-CoV-2 spike mutations and highlight a spike protein vulnerability that may be exploited to achieve broad protection against circulating variants. |
External links | Nat Commun / PubMed:35982054 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.16 - 3.21 Å |
Structure data | EMDB-27502, PDB-8dli: EMDB-27503, PDB-8dlj: EMDB-27504, PDB-8dlk: EMDB-27505, PDB-8dll: EMDB-27506, PDB-8dlm: EMDB-27507, PDB-8dln: EMDB-27508, PDB-8dlo: EMDB-27509, PDB-8dlp: EMDB-27510, PDB-8dlq: EMDB-27511: Cryo-EM structure of SARS-CoV-2 Gamma (P.1) spike protein in complex with Fab 4-8 EMDB-27512, PDB-8dlr: EMDB-27513: Cryo-EM structure of SARS-CoV-2 Gamma (P.1) spike protein in complex with Fab 4A8 EMDB-27514, PDB-8dls: EMDB-27515, PDB-8dlt: EMDB-27516, PDB-8dlu: EMDB-27517, PDB-8dlv: EMDB-27518, PDB-8dlw: EMDB-27519, PDB-8dlx: EMDB-27520, PDB-8dly: EMDB-27521, PDB-8dlz: EMDB-27522, PDB-8dm0: |
Chemicals | ChemComp-NAG: |
Source |
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Keywords | VIRAL PROTEIN / SARS-CoV-2 / glycoprotein / fusion protein / Viral Protein-Immune System complex / Alpha / B.1.1.7 / Viral Protein/Hydrolase / ACE2 / Viral Protein-Hydrolase complex / Beta / B.1.351 / Gamma / P.1 / 4-8 / 4A8 / Epsilon / B.1.429 / S2M11 / VH ab6 / VIRAL PROTEIN/IMMUNE SYSTEM |