7WXZ
Crystal structure of the recombinant protein HR121 from the S2 protein of SARS-CoV-2
Summary for 7WXZ
| Entry DOI | 10.2210/pdb7wxz/pdb |
| Descriptor | Spike protein S2' (2 entities in total) |
| Functional Keywords | sars-cov-2, s2, recombinant protein, hr121, fusion intermediate, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV,SARS-CoV-2) More |
| Total number of polymer chains | 4 |
| Total formula weight | 88826.71 |
| Authors | Zheng, Y.T.,Ouyang, S.,Pang, W.,Lu, Y.,Zhao, Y.B. (deposition date: 2022-02-15, release date: 2022-11-23, Last modification date: 2023-11-29) |
| Primary citation | Pang, W.,Lu, Y.,Zhao, Y.B.,Shen, F.,Fan, C.F.,Wang, Q.,He, W.Q.,He, X.Y.,Li, Z.K.,Chen, T.T.,Yang, C.X.,Li, Y.Z.,Xiao, S.X.,Zhao, Z.J.,Huang, X.S.,Luo, R.H.,Yang, L.M.,Zhang, M.,Dong, X.Q.,Li, M.H.,Feng, X.L.,Zhou, Q.C.,Qu, W.,Jiang, S.,Ouyang, S.,Zheng, Y.T. A variant-proof SARS-CoV-2 vaccine targeting HR1 domain in S2 subunit of spike protein. Cell Res., 32:1068-1085, 2022 Cited by PubMed Abstract: The emerging SARS-CoV-2 variants, commonly with many mutations in S1 subunit of spike (S) protein are weakening the efficacy of the current vaccines and antibody therapeutics. This calls for the variant-proof SARS-CoV-2 vaccines targeting the more conserved regions in S protein. Here, we designed a recombinant subunit vaccine, HR121, targeting the conserved HR1 domain in S2 subunit of S protein. HR121 consisting of HR1-linker1-HR2-linker2-HR1, is conformationally and functionally analogous to the HR1 domain present in the fusion intermediate conformation of S2 subunit. Immunization with HR121 in rabbits and rhesus macaques elicited highly potent cross-neutralizing antibodies against SARS-CoV-2 and its variants, particularly Omicron sublineages. Vaccination with HR121 achieved near-full protections against prototype SARS-CoV-2 infection in hACE2 transgenic mice, Syrian golden hamsters and rhesus macaques, and effective protection against Omicron BA.2 infection in Syrian golden hamsters. This study demonstrates that HR121 is a promising candidate of variant-proof SARS-CoV-2 vaccine with a novel conserved target in the S2 subunit for application against current and future SARS-CoV-2 variants. PubMed: 36357786DOI: 10.1038/s41422-022-00746-3 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.41 Å) |
Structure validation
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