ArticleScience advances2022
Probing the biophysical constraints of SARS-CoV-2 spike N-terminal domain using deep mutational scanning.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The trial behind it
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Who cites it
26 citing papers in PubMed.
- Strain-specific epistasis shapes fitness landscapes of APOBEC3G antagonism by HIV-1 Vif proteins.Science advances · 2026Article
- Deep mutational scanning of recent SARS-CoV-2 variants highlights changing amino acid preferences within epistatic hotspot residues.PLoS pathogens · 2026Article
- Article
- The Enigmatic Conserved Q134-F135-N137 Triad in SARS-CoV-2 Spike Protein: A Conformational Transducer?Biomolecules · 2026Review
- EZ-DMS - A Simple and Accessible Protocol and Software Package for Deep Mutational Scanning of Virus Proteins.bioRxiv : the preprint server for biology · 2026Article
- Insights from deep mutational scanning in the context of an emerging pathogen.Biochemical Society transactions · 2025Review
- Deep mutational scanning and CRISPR-engineered viruses: tools for evolutionary and functional genomics studies.mSphere · 2025Review
- Omicron-specific ultra-potent SARS-CoV-2 neutralizing antibodies targeting the N1/N2 loop of Spike N-terminal domain.Emerging microbes & infections · 2024Article
- Understanding epistatic networks in the B1 β-lactamases through coevolutionary statistical modeling and deep mutational scanning.Nature communications · 2024Article
- Deep mutational scanning of SARS-CoV-2 Omicron BA.2.86 and epistatic emergence of the KP.3 variant.bioRxiv : the preprint server for biology · 2024Article
- A library-on-library screen reveals the breadth expansion landscape of a broadly neutralizing betacoronavirus antibody.bioRxiv : the preprint server for biology · 2024Article
- Functional and antigenic characterization of SARS-CoV-2 spike fusion peptide by deep mutational scanning.Nature communications · 2024Article
- SARS-CoV-2 resistance to monoclonal antibodies and small-molecule drugs.Cell chemical biology · 2024Review
- Deep mutational scanning of SARS-CoV-2 Omicron BA.2.86 and epistatic emergence of the KP.3 variant.Virus evolution · 2024Article
- Mammalian Antigen Display for Pandemic Countermeasures.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Deep mutational scans of XBB.1.5 and BQ.1.1 reveal ongoing epistatic drift during SARS-CoV-2 evolution.PLoS pathogens · 2023Article
- Functional and antigenic characterization of SARS-CoV-2 spike fusion peptide by deep mutational scanning.bioRxiv : the preprint server for biology · 2023Article
- Deep mutational scanning of proteins in mammalian cells.Cell reports methods · 2023Review
- Deep mutational scans of XBB.1.5 and BQ.1.1 reveal ongoing epistatic drift during SARS-CoV-2 evolution.bioRxiv : the preprint server for biology · 2023Article
- Deep mutagenesis scanning using whole trimeric SARS-CoV-2 spike highlights the importance of NTD-RBD interactions in determining spike phenotype.PLoS pathogens · 2023Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Increasing the expression level of the SARS-CoV-2 spike (S) protein has been critical for COVID-19 vaccine development. While previous efforts largely focused on engineering the receptor-binding domain (RBD) and the S2 subunit, the amino-terminal domain (NTD) has been long overlooked because of the limited understanding of its biophysical constraints. In this study, the effects of thousands of NTD single mutations on S protein expression were quantified by deep mutational scanning. Our results revealed that in terms of S protein expression, the mutational tolerability of NTD residues was inversely correlated with their proximity to the RBD and S2. We also identified NTD mutations at the interdomain interface that increased S protein expression without altering its antigenicity. Overall, this study not only advances the understanding of the biophysical constraints of the NTD but also provides invaluable insights into S-based immunogen design.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.