7E7B

Cryo-EM structure of the SARS-CoV-2 furin site mutant S-Trimer from a subunit vaccine candidate

Summary for 7E7B

• Entry DOI: 10.2210/pdb7e7b/pdb
• EMDB information: 30998
• Descriptor: Spike glycoprotein,Collagen alpha-1(I) chain, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: spike protein, covid-19, vaccine, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); More
• Total number of polymer chains: 3
• Total formula weight: 526766.19

Authors

Zheng, S.,Ma, J. (deposition date: 2021-02-25, release date: 2021-03-24, Last modification date: 2022-12-07)

Primary citation

Ma, J.,Su, D.,Sun, Y.,Huang, X.,Liang, Y.,Fang, L.,Ma, Y.,Li, W.,Liang, P.,Zheng, S.
Cryo-EM structure of S-Trimer, a subunit vaccine candidate for COVID-19.
J.Virol., 95:-, 2021

PubMed Abstract: Within a year after its emergence, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 100 million people worldwide with a death toll over 2 million. Vaccination remains the best hope to ultimately put this pandemic to an end. Here, using Trimer-Tag technology, we produced both wild-type (WT) and furin site mutant (MT) S-Trimers for COVID-19 vaccine studies. Cryo-EM structures of the WT and MT S-Trimers, determined at 3.2 Å and 2.6 Å respectively, revealed that both antigens adopt a tightly closed conformation and their structures are essentially identical to that of the previously solved full-length WT S protein in detergent. The tightly closed conformation is stabilized by fatty acid and polysorbate 80 binding at the receptor binding domains (RBDs) and the N terminal domains (NTDs) respectively. Additionally, we identified an important pH switch in the WT S-Trimer that shows dramatic conformational change and accounts for its increased stability at lower pH. These results validate Trimer-Tag as a platform technology in production of metastable WT S-Trimer as a candidate for COVID-19 subunit vaccine.Effective vaccine against SARS-CoV-2 is critical to end the COVID-19 pandemic. Here, using Trimer-Tag technology, we are able to produce stable and large quantities of WT S-Trimer, a subunit vaccine candidate for COVID-19 with high safety and efficacy from animal and Phase 1 clinical trial studies. Cryo-EM structures of the S-Trimer subunit vaccine candidate show that it predominately adopts tightly closed pre-fusion state, and resembles that of the native and full-length spike in detergent, confirming its structural integrity. WT S-Trimer is currently being evaluated in global Phase 2/3 clinical trial. Combining with published structures of the S protein, we also propose a model to dissect the conformation change of the spike protein before receptor binding.

PubMed: 33692215
DOI: 10.1128/JVI.00194-21

Experimental method

ELECTRON MICROSCOPY (2.6 Å)