7WXZ

Crystal structure of the recombinant protein HR121 from the S2 protein of SARS-CoV-2

7WXZ の概要

• エントリーDOI: 10.2210/pdb7wxz/pdb
• 分子名称: Spike protein S2' (2 entities in total)
• 機能のキーワード: sars-cov-2, s2, recombinant protein, hr121, fusion intermediate, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV,SARS-CoV-2); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 88826.71

構造登録者

Zheng, Y.T.,Ouyang, S.,Pang, W.,Lu, Y.,Zhao, Y.B. (登録日: 2022-02-15, 公開日: 2022-11-23, 最終更新日: 2023-11-29)

主引用文献

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

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: 36357786
DOI: 10.1038/s41422-022-00746-3

実験手法

X-RAY DIFFRACTION (2.41 Å)