9UE7
Cryo-EM structure of SARS-CoV-2 KP.2 spike in complex with ACE2
Summary for 9UE7
| Entry DOI | 10.2210/pdb9ue7/pdb |
| EMDB information | 64078 |
| Descriptor | Angiotensin-converting enzyme 2, Spike glycoprotein (2 entities in total) |
| Functional Keywords | spike and ace2 complex, viral protein/hydrolase, viral protein-hydrolase complex |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 6 |
| Total formula weight | 652767.61 |
| Authors | |
| Primary citation | Shi, J.,Zhao, X.,Jin, X.,Li, J.,Liu, Y.,Liu, H.,Hu, Y.F.,Chen, Z.,Xiao, Y.,Wang, L.,Wang, Y.,He, Y.,Chai, Y.,Hu, B.,Shuai, H.,Wang, Y.,Li, X.,Jiang, S.,Zhang, Y.,Zhang, X.,Chan, W.M.,Chen, L.L.,Cai, J.P.,Sui, B.,Zhang, H.,Yang, D.,Zhu, L.,Yuan, S.,Zhou, J.,Huang, J.D.,Yuen, K.Y.,To, K.K.,Chan, J.F.,Zhang, B.Z.,Wang, Q.,He, M.,Sun, L.,Wang, P.,Chu, H. Pathogenicity, virological features, and immune evasion of SARS-CoV-2 JN.1-derived variants including JN.1.7, KP.2, KP.3, and KP.3.1.1. Nat Commun, 16:11002-11002, 2025 Cited by PubMed Abstract: KP.3.1.1 became a dominant successor to JN.1 by the second half of 2024 but the intrinsic pathogenicity and virological feature of KP.3.1.1 remain incompletely understood. Here, we comprehensively evaluated the pathogenesis and characteristics of KP.3.1.1 in comparison to JN.1 and other JN.1-derived variants including JN.1.7, KP.2, and KP.3. The unique S31del mutation on KP.3.1.1 spike confers further evasion to the clinically authorized mAb Pemivibart and reduces convalescent serum neutralization efficiency. Structural analysis indicates that S31del induces novel glycosylation sites that facilitates evasion of neutralizing antibodies. We further reveal that S31del significantly enhances pseudovirus entry efficiency in all evaluated cell types including the human primary nasal epithelial cells. Nevertheless, the intrinsic pathogenicity of KP.3.1.1 is similar to JN.1 and KP.3, and higher than that of JN.1.7 and KP.2 in a male hamster model. Interestingly, the increased virus infectivity conferred by S31del in KP.3.1.1 spike is counterbalanced by the NSP10 S33C mutation. Overall, our study indicates that a single spike mutation can confer both enhanced immune escape and increased viral infectivity. The opposing effects of spike and non-spike mutations highlight the complex interplay of viral genomic elements in shaping their overall fitness, and reveal the high plasticity of coronavirus evolution. PubMed: 41381428DOI: 10.1038/s41467-025-66018-x PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.27 Å) |
Structure validation
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