8JYS
SARS-CoV-2 Spike RBD (dimer) in complex with two 2S-1244 nanobodies
Summary for 8JYS
| Entry DOI | 10.2210/pdb8jys/pdb |
| EMDB information | 36730 |
| Descriptor | IBT-CoV144 nanobody, Spike protein S1 (2 entities in total) |
| Functional Keywords | spike, nanobody, dimer, local, viral protein |
| Biological source | Camelus bactrianus More |
| Total number of polymer chains | 4 |
| Total formula weight | 75416.53 |
| Authors | Yang, Y.,Zhang, C.H. (deposition date: 2023-07-03, release date: 2024-06-12, Last modification date: 2024-11-06) |
| Primary citation | Yang, Y.,Zhang, J.,Zhang, S.,Zhang, C.,Shen, C.,Song, S.,Wang, Y.,Peng, Y.,Gong, X.,Dai, J.,Xie, C.,Khrustaleva, T.A.,Khrustalev, V.V.,Huo, Y.,Lu, D.,Yao, D.,Zhao, J.,Liu, Y.,Lu, H. A novel nanobody broadly neutralizes SARS-CoV-2 via induction of spike trimer dimers conformation. Exploration (Beijing), 4:20230086-20230086, 2024 Cited by PubMed Abstract: The ongoing mutations of the SARS-CoV-2 pose serious challenges to the efficacy of the available antiviral drugs, and new drugs with fantastic efficacy are always deserved investigation. Here, a nanobody called IBT-CoV144 is reported, which exhibits broad neutralizing activity against SARS-CoV-2 by inducing the conformation of spike trimer dimers. IBT-CoV144 was isolated from an immunized alpaca using the RBD of wild-type SARS-CoV-2, and it showed strong cross-reactive binding and neutralizing potency against diverse SARS-CoV-2 variants, including Omicron subvariants. Moreover, the prophylactically and therapeutically intranasal administration of IBT-CoV144 confers fantastic protective efficacy against the challenge of Omicron BA.1 variant in BALB/c mice model. The structure analysis of the complex between spike (S) protein, conducted using Cryo-EM, revealed a special conformation known as the trimer dimers. This conformation is formed by two trimers, with six RBDs in the "up" state and bound by six VHHs. IBT-CoV144 binds to the lateral region of the RBD on the S protein, facilitating the aggregation of S proteins. This aggregation results in steric hindrance, which disrupts the recognition of the virus by ACE2 on host cells. The discovery of IBT-CoV144 will provide valuable insights for the development of advanced therapeutics and the design of next-generation vaccines. PubMed: 38939869DOI: 10.1002/EXP.20230086 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.5 Å) |
Structure validation
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