bioRxivBioinformaticsPreprint
The high infectivity of SARS-CoV-2 B.1.1.7 is associated with increased interaction force between Spike-ACE2 caused by the viral N501Y mutation
Abstract
The Spike glycoprotein receptor-binding domain (RBD) of SARS-CoV-2 mediates the viral particles binding to the angiotensin-converting enzyme 2 (ACE2) receptor on the surface of human cells. Therefore, Spike-ACE2 interaction is a crucial determining factor for viral infectivity. A new phylogenetic group of SARS-CoV-2 (lineage B.1.1.7) has been recently identified in the COVID-19 Genomics UK Consortium dataset, which features an amino acid substitution in the Spike RBD (N501Y mutation). Infections with the SARS-CoV-2 lineage B.1.1.7 have been overgrowing in recent weeks in the United Kingdom, indicating an even greater spread capacity than that seen with previous strains of the novel coronavirus. We hypothesized that this rapid spreading/infectivity of the B.1.1.7 lineage might be due to changes in the interaction force between the mutant Spike RBD and ACE2. This study employed in silico methods involving mutagenesis (N501Y mutation) and interface analysis focusing on the Spike RDB-ACE2 interaction. The results showed that the SARS-CoV-2 N501Y mutant (lineage B.1.1.7) establishes a more significant number of interactions relating to the mutant residue Y501 (Spike RDB) with residues Y41 and K353 (ACE2). This finding shows that the increased infectivity of SARS-CoV-2 lineage B.1.1.7 is associated with the interaction force between the Spike RBD Y501 mutant residue with the ACE2 receptor, which in this strain is increased.
- organism: human
- assay: proteomics
- research focus: protein structure prediction
- research focus: protein design
- research focus: benchmarking
- approach: statistical model
- approach: simulation
Abstract summary
Claude Opus 5.5 · xhigh effort · 2 Nov 2026 · from the abstract · CC BY-NC-ND 4.0
In silico mutagenesis and interface analysis indicate that the SARS-CoV-2 lineage B.1.1.7 Spike N501Y substitution increases intermolecular contacts with human ACE2 residues Y41 and K353.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.1.7, carrying the N501Y substitution in the Spike receptor-binding domain (RBD), has spread rapidly in the United Kingdom. Computational mutagenesis and interface analysis test whether N501Y strengthens the interaction between the viral Spike RBD and human angiotensin-converting enzyme 2 (ACE2).
Key results
SuggestedThe SARS-CoV-2 lineage B.1.1.7 N501Y substitution increases the number of intermolecular interactions and interaction force between Spike RBD residue Y501 and human ACE2 residues Y41 and K353.
In silico mutagenesis of N501Y and structural interface analysis of the Spike RBD-ACE2 complex; specific contact counts and binding energy values are not provided in the abstract. · Abstract
Methods, data and reproducibility
The authors performed in silico mutagenesis to introduce the lineage B.1.1.7 N501Y substitution into the SARS-CoV-2 Spike receptor-binding domain (RBD) and conducted computational interface analysis of its contacts with human ACE2, focusing on interactions involving residue Y501 with ACE2 residues Y41 and K353.
- Structural model of the SARS-CoV-2 Spike receptor-binding domain bound to human ACE2 (with lineage B.1.1.7 identified in the COVID-19 Genomics UK Consortium dataset) · SARS-CoV-2, human
- Reproducibility gaps
- Protein Data Bank (PDB) structure identifiers, mutagenesis and interface analysis software names, and code are not stated in the abstract.
Limitations (2)
- Findings rely exclusively on in silico mutagenesis and interface analysis without experimental binding or infectivity assays. · noted in this summary
- Abstract only; specific software tools, structural template accessions, contact counts, and energetic values are not reported. · noted in this summary
Read this if you study how the N501Y Spike receptor-binding domain mutation in SARS-CoV-2 lineage B.1.1.7 alters structural contacts with human ACE2.
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- 90
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