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| Title | Structural and functional insights into the evolution of SARS-CoV-2 KP.3.1.1 spike protein. |
|---|---|
| Journal, issue, pages | Cell Rep, Vol. 44, Issue 7, Page 115941, Year 2025 |
| Publish date | Jul 4, 2025 |
 Authors | Ziqi Feng / Jiachen Huang / Sabyasachi Baboo / Jolene K Diedrich / Sandhya Bangaru / James C Paulson / John R Yates / Meng Yuan / Ian A Wilson / Andrew B Ward /  |
| PubMed Abstract | The JN.1-sublineage KP.3.1.1 recently emerged as the globally prevalent SARS-CoV-2 variant, demonstrating increased infectivity and antibody escape. We investigate how mutations and a deletion in the ...The JN.1-sublineage KP.3.1.1 recently emerged as the globally prevalent SARS-CoV-2 variant, demonstrating increased infectivity and antibody escape. We investigate how mutations and a deletion in the KP.3.1.1 spike protein (S) affect hACE2 binding and antibody escape. Mass spectrometry confirms a new glycan site at residue N30 that alters the glycoforms at neighboring N61. Cryoelectron microscopy (cryo-EM) structures show that the N30 glycan and rearrangement of adjacent residues do not significantly change the overall spike structure, up-down ratio of receptor-binding domains (RBDs), or hACE2 binding. Furthermore, a KP.3.1.1 S with hACE2 structure further confirms an epistatic effect between F456L and Q493E on hACE2 binding. Our analysis shows that SARS-CoV-2 variants that emerged after late 2023 are now incorporating reversions to residues found in other sarbecoviruses, including the N30 glycan, Q493E, and others. Overall, these results inform on the structural and functional consequences of the KP.3.1.1 mutations, the current SARS-CoV-2 evolutionary trajectory, and immune evasion. |
 External links | Cell Rep / PubMed:40618371 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.64 - 3.71 Å |
| Structure data | EMDB-48146, PDB-9ele: EMDB-48147, PDB-9elf: EMDB-48148, PDB-9elg: EMDB-48149, PDB-9elh: EMDB-48150, PDB-9eli: EMDB-48151, PDB-9elj: EMDB-48152, PDB-9elk: EMDB-48153, PDB-9ell: EMDB-48155, PDB-9elm: EMDB-48156, PDB-9eln: EMDB-48157, PDB-9elo: EMDB-48158, PDB-9elp: EMDB-48159, PDB-9elq:  EMDB-49904: KP.3.1.1 spike with 2 missing RBDs  EMDB-49905: JN.1.11+Q493E+S31deletion spike with 1 missing RBD  EMDB-49906: JN.1.11 spike with 1 missing RBD  EMDB-49907: JN.1.11+S31deletion spike with 1 missing RBD  EMDB-49908: JN.1.11.1+S31deletion spike with 2 missing RBDs |
| Chemicals |  ChemComp-NAG: |
| Source |
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 Keywords | VIRAL PROTEIN / SARS-CoV-2 / COVID-19 / hACE2 / RBD / Spike |
homo sapiens (human)
severe acute respiratory syndrome coronavirus 2