8YDQ
Crystal structure of the receptor binding domain of SARS-CoV-2 Omicron BA.2 variant spike protein in complex with Ce149
Summary for 8YDQ
| Entry DOI | 10.2210/pdb8ydq/pdb |
| Descriptor | SARS-CoV-2 inhibiting peptide Ce149, Spike protein S1, GLYCEROL, ... (4 entities in total) |
| Functional Keywords | rbd, viral protein-inhibitor complex, viral protein/inhibitor |
| Biological source | Severe acute respiratory syndrome coronavirus 2 More |
| Total number of polymer chains | 2 |
| Total formula weight | 31168.92 |
| Authors | Nakamura, S.,Numoto, N.,Fujiyoshi, Y. (deposition date: 2024-02-21, release date: 2025-01-15, Last modification date: 2025-07-30) |
| Primary citation | Nakamura, S.,Tanimura, Y.,Nomura, R.,Suzuki, H.,Nishikawa, K.,Kamegawa, A.,Numoto, N.,Tanaka, A.,Kawabata, S.,Sakaguchi, S.,Emi, A.,Suzuki, Y.,Fujiyoshi, Y. Structure-guided engineering of a mutation-tolerant inhibitor peptide against variable SARS-CoV-2 spikes. Proc.Natl.Acad.Sci.USA, 122:e2413465122-e2413465122, 2025 Cited by PubMed Abstract: Pathogen mutations present an inevitable and challenging problem for therapeutics and the development of mutation-tolerant anti-infective drugs to strengthen global health and combat evolving pathogens is urgently needed. While spike proteins on viral surfaces are attractive targets for preventing viral entry, they mutate frequently, making it difficult to develop effective therapeutics. Here, we used a structure-guided strategy to engineer an inhibitor peptide against the SARS-CoV-2 spike, called CeSPIACE, with mutation-tolerant and potent binding ability against all variants to enhance affinity for the invariant architecture of the receptor-binding domain (RBD). High-resolution structures of the peptide complexed with mutant RBDs revealed a mechanism of mutation-tolerant inhibition. CeSPIACE bound major mutant RBDs with picomolar affinity and inhibited infection by SARS-CoV-2 variants in VeroE6/TMPRSS2 cells (IC 4 pM to 13 nM) and demonstrated potent in vivo efficacy by inhalation administration in hamsters. Mutagenesis analyses to address mutation risks confirmed tolerance against existing and/or potential future mutations of the RBD. Our strategy of engineering mutation-tolerant inhibitors may be applicable to other infectious diseases. PubMed: 39854234DOI: 10.1073/pnas.2413465122 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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