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Structure paper

TitleStructural and biochemical rationale for enhanced spike protein fitness in delta and kappa SARS-CoV-2 variants.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 742, Year 2022
Publish dateFeb 8, 2022
AuthorsJames W Saville / Dhiraj Mannar / Xing Zhu / Shanti S Srivastava / Alison M Berezuk / Jean-Philippe Demers / Steven Zhou / Katharine S Tuttle / Inna Sekirov / Andrew Kim / Wei Li / Dimiter S Dimitrov / Sriram Subramaniam /
PubMed AbstractThe Delta and Kappa variants of SARS-CoV-2 co-emerged in India in late 2020, with the Delta variant underlying the resurgence of COVID-19, even in countries with high vaccination rates. In this ...The Delta and Kappa variants of SARS-CoV-2 co-emerged in India in late 2020, with the Delta variant underlying the resurgence of COVID-19, even in countries with high vaccination rates. In this study, we assess structural and biochemical aspects of viral fitness for these two variants using cryo-electron microscopy (cryo-EM), ACE2-binding and antibody neutralization analyses. Both variants demonstrate escape of antibodies targeting the N-terminal domain, an important immune hotspot for neutralizing epitopes. Compared to wild-type and Kappa lineages, Delta variant spike proteins show modest increase in ACE2 affinity, likely due to enhanced electrostatic complementarity at the RBD-ACE2 interface, which we characterize by cryo-EM. Unexpectedly, Kappa variant spike trimers form a structural head-to-head dimer-of-trimers assembly, which we demonstrate is a result of the E484Q mutation and with unknown biological implications. The combination of increased antibody escape and enhanced ACE2 binding provides an explanation, in part, for the rapid global dominance of the Delta variant.
External linksNat Commun / PubMed:35136050 / PubMed Central
MethodsEM (single particle)
Resolution2.25 - 3.62 Å
Structure data

EMDB-25853, PDB-7tew:
Cryo-EM structure of SARS-CoV-2 Delta (B.1.617.2) spike protein in complex with human ACE2 (focused refinement of RBD and ACE2)
Method: EM (single particle) / Resolution: 3.52 Å

EMDB-25854, PDB-7tex:
Cryo-EM structure of SARS-CoV-2 Delta (B.1.617.2) spike protein in complex with human ACE2
Method: EM (single particle) / Resolution: 3.27 Å

EMDB-25855, PDB-7tey:
Cryo-EM structure of SARS-CoV-2 Delta (B.1.617.2) spike protein
Method: EM (single particle) / Resolution: 2.25 Å

EMDB-25856, PDB-7tez:
Cryo-EM structure of SARS-CoV-2 Kappa (B.1.617.1) spike protein in complex with human ACE2 (focused refinement of RBD and ACE2)
Method: EM (single particle) / Resolution: 3.27 Å

EMDB-25857, PDB-7tf0:
Cryo-EM structure of SARS-CoV-2 Kappa (B.1.617.1) spike protein in complex with human ACE2
Method: EM (single particle) / Resolution: 3.02 Å

EMDB-25858, PDB-7tf1:
Cryo-EM structure of SARS-CoV-2 Kappa (B.1.617.1) Q484I spike protein (focused refinement of RBD)
Method: EM (single particle) / Resolution: 3.57 Å

EMDB-25859, PDB-7tf2:
Cryo-EM structure of SARS-CoV-2 Kappa (B.1.617.1) Q484I spike protein
Method: EM (single particle) / Resolution: 3.62 Å

EMDB-25860, PDB-7tf3:
Cryo-EM structure of SARS-CoV-2 Kappa (B.1.617.1) Q484A spike protein
Method: EM (single particle) / Resolution: 2.25 Å

EMDB-25861, PDB-7tf4:
Cryo-EM structure of SARS-CoV-2 Kappa (B.1.617.1) spike protein (focused refinement of RBD)
Method: EM (single particle) / Resolution: 3.01 Å

EMDB-25862, PDB-7tf5:
Cryo-EM structure of SARS-CoV-2 Kappa (B.1.617.1) spike protein
Method: EM (single particle) / Resolution: 3.16 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / SARS-CoV-2 / glycoprotein / fusion protein / ACE2

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