ArticleMolecules (Basel, Switzerland)2021
D936Y and Other Mutations in the Fusion Core of the SARS-CoV-2 Spike Protein Heptad Repeat 1: Frequency, Geographical Distribution, and Structural Effect.
Article in Molecules (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- SARS-CoV-2 Spike Protein XBB.1.5 Mutations Altered Four Conserved Antigenic Determinants.International journal of molecular sciences · 2026Article
- COVID-19 Variants and Vaccine Development.Viruses · 2024Review
- Ensemble-Based Mutational Profiling and Network Analysis of the SARS-CoV-2 Spike Omicron XBB Lineages for Interactions with the ACE2 Receptor and Antibodies: Cooperation of Binding Hotspots in Mediating Epistatic Couplings Underlies Binding Mechanism and Immune Escape.International journal of molecular sciences · 2024Article
- High fusion and cytopathy of SARS-CoV-2 variant B.1.640.1.Journal of virology · 2024Article
- Structural and pKa Estimation of the Amphipathic HR1 in SARS-CoV-2: Insights from Constant pH MD, Linear vs. Nonlinear Normal Mode Analysis.International journal of molecular sciences · 2023Article
- Antitarget, Anti-SARS-CoV-2 Leads, Drugs, and the Drug Discovery-Genetics Alliance Perspective.Journal of medicinal chemistry · 2023Review
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- The phylodynamics of SARS-CoV-2 during 2020 in Finland.Communications medicine · 2022Article
- Heptad stereotypy, S/Q layering, and remote origin of the SARS-CoV-2 fusion core.Virus evolution · 2022Article
- Immunoinformatics Aided Design andFrontiers in immunology · 2022Article
- Community-level SARS-CoV-2 sequence diversity revealed by wastewater sampling.The Science of the total environment · 2021Article
- Genomic diversity of SARS-CoV-2 in Oxford during United Kingdom's first national lockdown.Scientific reports · 2021Article
- Therapeutic targets and interventional strategies in COVID-19: mechanisms and clinical studies.Signal transduction and targeted therapy · 2021Review
- An engineered CRISPR-Cas12a variant and DNA-RNA hybrid guides enable robust and rapid COVID-19 testing.Nature communications · 2021Article
- Functional and druggability analysis of the SARS-CoV-2 proteome.European journal of pharmacology · 2021Article
- Growth, Antigenicity, and Immunogenicity of SARS-CoV-2 Spike Variants Revealed by a Live rVSV-SARS-CoV-2 Virus.Frontiers in medicine · 2021Article
- SARS-CoV-2 growth, furin-cleavage-site adaptation and neutralization using serum from acutely infected hospitalized COVID-19 patients.The Journal of general virology · 2020Article
- Spatio-Temporal Mutational Profile Appearances of Swedish SARS-CoV-2 during the Early Pandemic.Viruses · 2020Article
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5 authors.
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No grant is acknowledged in the PubMed record.
Abstract
The crown of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is constituted by its spike (S) glycoprotein. S protein mediates the SARS-CoV-2 entry into the host cells. The "fusion core" of the heptad repeat 1 (HR1) on S plays a crucial role in the virus infectivity, as it is part of a key membrane fusion architecture. While SARS-CoV-2 was becoming a global threat, scientists have been accumulating data on the virus at an impressive pace, both in terms of genomic sequences and of three-dimensional structures. On 15 February 2021, from the SARS-CoV-2 genomic sequences in the GISAID resource, we collected 415,673 complete S protein sequences and identified all the mutations occurring in the HR1 fusion core. This is a 21-residue segment, which, in the post-fusion conformation of the protein, gives many strong interactions with the heptad repeat 2, bringing viral and cellular membranes in proximity for fusion. We investigated the frequency and structural effect of novel mutations accumulated over time in such a crucial region for the virus infectivity. Three mutations were quite frequent, occurring in over 0.1% of the total sequences. These were S929T, D936Y, and S949F, all in the N-terminal half of the HR1 fusion core segment and particularly spread in Europe and USA. The most frequent of them, D936Y, was present in 17% of sequences from Finland and 12% of sequences from Sweden. In the post-fusion conformation of the unmutated S protein, D936 is involved in an inter-monomer salt bridge with R1185. We investigated the effect of the D936Y mutation on the pre-fusion and post-fusion state of the protein by using molecular dynamics, showing how it especially affects the latter one.
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