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TitleSpike structures, receptor binding, and immune escape of recently circulating SARS-CoV-2 Omicron BA.2.86, JN.1, EG.5, EG.5.1, and HV.1 sub-variants.
Journal, issue, pagesStructure, Vol. 32, Issue 8, Page 1055-11067.e6, Year 2024
Publish dateAug 8, 2024
AuthorsLinjie Li / Kaiyuan Shi / Yuhang Gu / Zepeng Xu / Chang Shu / Dedong Li / Junqing Sun / Mengqing Cong / Xiaomei Li / Xin Zhao / Guanghui Yu / Songnian Hu / Hui Tan / Jianxun Qi / Xiaopeng Ma / Kefang Liu / George F Gao /
PubMed AbstractThe recently emerged BA.2.86, JN.1, EG.5, EG.5.1, and HV.1 variants have a growth advantage. In this study, we explore the structural bases of receptor binding and immune evasion for the Omicron BA.2. ...The recently emerged BA.2.86, JN.1, EG.5, EG.5.1, and HV.1 variants have a growth advantage. In this study, we explore the structural bases of receptor binding and immune evasion for the Omicron BA.2.86, JN.1, EG.5, EG.5.1, and HV.1 sub-variants. Our findings reveal that BA.2.86 exhibits strong receptor binding, whereas its JN.1 sub-lineage displays a decreased binding affinity to human ACE2 (hACE2). Through complex structure analyses, we observed that the reversion of R493Q in BA.2.86 receptor binding domain (RBD) plays a facilitating role in receptor binding, while the L455S substitution in JN.1 RBD restores optimal affinity. Furthermore, the structure of monoclonal antibody (mAb) S309 complexed with BA.2.86 RBD highlights the importance of the K356T mutation, which brings a new N-glycosylation motif, altering the binding pattern of mAbs belonging to RBD-5 represented by S309. These findings emphasize the importance of closely monitoring BA.2.86 and its sub-lineages to prevent another wave of SARS-CoV-2 infections.
External linksStructure / PubMed:39013463
MethodsEM (single particle)
Resolution2.61 - 3.31 Å
Structure data

EMDB-38460, PDB-8xlv:
Cryo-EM structure of SARS-CoV-2 Omicron BA.2.86 spike protein(6P), 1-RBD-up state
Method: EM (single particle) / Resolution: 3.07 Å

EMDB-38463, PDB-8xm5:
Cryo-EM structure of SARS-CoV-2 Omicron EG.5 spike protein(6P), RBD-closed state
Method: EM (single particle) / Resolution: 2.61 Å

EMDB-38476, PDB-8xmg:
Cryo-EM structure of SARS-CoV-2 Omicron HV.1 spike protein(6P), RBD-closed state
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-38488, PDB-8xmt:
Cryo-EM structure of SARS-CoV-2 Omicron EG.5.1 spike protein(6P), RBD-closed state
Method: EM (single particle) / Resolution: 3.31 Å

EMDB-38495, PDB-8xn2:
SARS-CoV-2 Omicron EG.5.1 RBD in complex with human ACE2 (local refined from the spike protein)
Method: EM (single particle) / Resolution: 2.79 Å

EMDB-38496, PDB-8xn3:
SARS-CoV-2 Omicron HV.1 RBD in complex with human ACE2 (local refinement from the spike protein)
Method: EM (single particle) / Resolution: 2.64 Å

EMDB-38498, PDB-8xn5:
Cryo-EM structure of SARS-CoV-2 Omicron EG.5.1 spike protein(6P) in complex with human ACE2
Method: EM (single particle) / Resolution: 2.87 Å

EMDB-38502, PDB-8xnf:
Cryo-EM structure of SARS-CoV-2 Omicron BA.2.86 spike protein(6P) in complex with human ACE2
Method: EM (single particle) / Resolution: 3.26 Å

EMDB-38505, PDB-8xnk:
Cryo-EM structure of SARS-CoV-2 Omicron HV.1 spike protein(6P) in complex with human ACE2
Method: EM (single particle) / Resolution: 2.78 Å

EMDB-38826, PDB-8y16:
Cryo-EM structure of SARS-CoV-2 Omicron JN.1 spike protein in complex with human ACE2
Method: EM (single particle) / Resolution: 2.98 Å

EMDB-38827, PDB-8y18:
Cryo-EM structure of SARS-CoV-2 Omicron JN.1 RBD in complex with human ACE2 (local refinement from the spike protein)
Method: EM (single particle) / Resolution: 3.04 Å

EMDB-38937, PDB-8y5j:
Cryo-EM structure of SARS-CoV-2 Omicron JN.1 spike protein
Method: EM (single particle) / Resolution: 2.94 Å

EMDB-38983, PDB-8y6a:
Cryo-EM structure of SARS-CoV-2 Omicron BA.2.86 RBD in complex with human ACE2 and S309 Fab
Method: EM (single particle) / Resolution: 2.72 Å

Chemicals

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

ChemComp-ZN:
Unknown entry

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / SARS-CoV-2 / Omicron / BA.2.86 / spike protein / EG.5 / HV.1 / EG.5.1 / HYDROLASE/VIRAL PROTEIN / human ACE2 / RBD / HYDROLASE-VIRAL PROTEIN complex / JN.1 / VIRUS / VIRAL PROTEIN/IMMUNE SYSTEM / S309 / hACE2 / VIRAL PROTEIN-IMMUNE SYSTEM complex

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