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Authors: Yongfei Cai, Jun Zhang, Tianshu Xiao1, Hanqin Peng, Sarah M. Sterling, Richard M. Walsh Jr., Shaun Rawson, Sophia Rits-Volloch, Bing Chen.

Link to paper: https://www.biorxiv.org/content/10.1101/2020.05.16.099317v1.full.pdf

Journal/ Pre-Print: bioRvix

Tags: Immunology/Immunity, Vaccines, Virology

Research Highlights

1. Two cryo-EM structures of the spike protein in pre-fusion and post-fusion confirmation.

2. Changes of the structural conformation from pre- to post-fusion are independent of target cells.

3. N-linked glycans on the S ectodomain trimer suggest possible mechanism of host immune evasion.

Summary 

Two states of the SARS-CoV-2 spike (S) protein was determined by cryo-EM presenting a pre-fusion and post-fusion state, expressed and purified from a single preparation solubilized in detergent. The S protein is produced as a precursor trimer and undergoes cleavage by potentially furin-like protease into a receptor-binding fragment S1 and the fusion fragment S2. The authors suggest that pre- and post-fusion spikes are present on mature virions, in which post-fusion spikes are formed by S2 after S1 dissociates in the absence of ACE2. Additionally, the post-fusion trimer displays a stable and rigid structure, with some shielding by N-linked glycans along its axis suggesting possible mechanism of evading of host immune response and external conditions.

Impact for SARS-CoV2/COVID19 research efforts

Develop a vaccine for SARS-CoV2/COVID19

Study Type

· In vitro study

Strengths and limitations of the paper

Novelty: There are a number of structural papers examining the Spike protein and there are a few potentially important differences highlighted especially regarding what may aid trimer stability and post fusion structures.

Standing in the field: Builds on previous structures but does highlight differences.

Appropriate statistics: Yes

Viral model used: Full-length spike (S) protein (residue 1-1273) of SARS-CoV-2 expressed in Expi293 HEK cells.

Translatability: Important for vaccine design

Main limitations: The structures are very interesting and extremely useful tool for vaccine design for example key salt bridges in the trimer are identified. The post- and pre-fusion structures allow the authors to hypothesis some interesting ideas about immunomodulation, viral cell entry and basic cell biology of this virus and its life cycle. However, as they realise there is a requirement for a lot of further studies to demonstrate a lot of these finding in terms of the biology discussed. Indeed a structure of the S protein in a viral membrane is of great importance to further elucidate these ideas.