ArticleNature communications2023
High-throughput identification of prefusion-stabilizing mutations in SARS-CoV-2 spike.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Scanning the horizon: deep mutational scanning approaches in virology.Journal of virology · 2026Review
- Systematic investigation of double emulsion dewetting dynamics for the robust production of giant unilamellar vesicles.Lab on a chip · 2026Article
- Repeated COVID-19 vaccine boosters elicit variant-specific memory B cells in humans.Cell reports · 2026Article
- Functional and antigenic constraints on the Nipah virus fusion protein.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A Mammalian Surface Display Platform to Optimize the Antigenicity of Viral Proteins for Vaccine Design.bioRxiv : the preprint server for biology · 2026Article
- Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026Review
- Cavity-Filling Mutations as a Strategy to Stabilize Prefusion Viral Fusion Proteins for Vaccine Design.Computational and structural biotechnology journal · 2026Review
- Functional and antigenic constraints on the Nipah virus fusion protein.bioRxiv : the preprint server for biology · 2026Article
- Structure-Guided Design of Peptide Inhibitors Targeting Class I Viral Fusion Proteins.Pathogens (Basel, Switzerland) · 2025Review
- Spike mutations that affect the function and antigenicity of recent KP.3.1.1-like SARS-CoV-2 variants.Journal of virology · 2025Article
- Antigen Format Determines Immunogenicity of AAV-Based SARS-CoV-2 Vaccines: Full-Length Spike Versus Truncated Subunits.Vaccines · 2025Article
- Insights from deep mutational scanning in the context of an emerging pathogen.Biochemical Society transactions · 2025Review
- Unique Features and Collateral Immune Effects of mRNA-LNP COVID-19 Vaccines: Plausible Mechanisms of Adverse Events and Complications.Pharmaceutics · 2025Review
- Spike mutations that affect the function and antigenicity of recent KP.3.1.1-like SARS-CoV-2 variants.bioRxiv : the preprint server for biology · 2025Article
- Molecular mechanisms of SARS-CoV-2 entry: implications for biomedical strategies.Microbiology and molecular biology reviews : MMBR · 2025Review
- Stabilization of norovirus GII.3 virus-like particles by rational disulfide engineering.NPJ vaccines · 2025Article
- Establishing correlation between in vitro potency and in vivo immunogenicity for mRNA vaccines.NPJ vaccines · 2025Review
- Capture of fusion-intermediate conformations of SARS-CoV-2 spike requires receptor binding and cleavage at either the S1/S2 or S2' site.PLoS pathogens · 2025Article
- Article
- Direct Mapping of Polyclonal Epitopes in Serum by HDX-MS.Analytical chemistry · 2024Article
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12 authors.
Funding
Abstract
Designing prefusion-stabilized SARS-CoV-2 spike is critical for the effectiveness of COVID-19 vaccines. All COVID-19 vaccines in the US encode spike with K986P/V987P mutations to stabilize its prefusion conformation. However, contemporary methods on engineering prefusion-stabilized spike immunogens involve tedious experimental work and heavily rely on structural information. Here, we establish a systematic and unbiased method of identifying mutations that concomitantly improve expression and stabilize the prefusion conformation of the SARS-CoV-2 spike. Our method integrates a fluorescence-based fusion assay, mammalian cell display technology, and deep mutational scanning. As a proof-of-concept, we apply this method to a region in the S2 domain that includes the first heptad repeat and central helix. Our results reveal that besides K986P and V987P, several mutations simultaneously improve expression and significantly lower the fusogenicity of the spike. As prefusion stabilization is a common challenge for viral immunogen design, this work will help accelerate vaccine development against different viruses.
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