UK Variants-B.1.1.7 and B.1.525

B.1.1.7 lineage (a.k.a. 20I/501Y.V1 Variant of Concern (VOC) 202012/01) - source CDC.gov

This variant has a mutation in the receptor binding domain (RBD) of the spike protein at position 501, where the amino acid asparagine (N) has been replaced with tyrosine (Y). The shorthand for this mutation is N501Y. This variant also has several other mutations, including:
- 69/70 deletion: occurred spontaneously many times and likely leads to a conformational change in the spike protein
- P681H: near the S1/S2 furin cleavage site, a site with high variability in coronaviruses. This mutation has also emerged spontaneously multiple times.
This variant is estimated to have first emerged in the UK during September 2020.
Since December 20, 2020, several countries have reported cases of the B.1.1.7 lineage, including the United States.
This variant is associated with increased transmissibility (i.e., more efficient and rapid transmission).
In January 2021, scientists from UK reported evidence[1] that suggests the B.1.1.7 variant may be associated with an increased risk of death compared with other variants.
Early reports found no evidence to suggest that the variant has any impact on the severity of disease or vaccine efficacy. source

N501Y, enhances spike binding at the human ACE2 cell receptor

Molecular Mechanism of the N501Y Mutation for Enhanced Binding between SARS-CoV-2’s Spike Protein and Human ACE2 Receptor

"...Using all atom molecular dynamics simulations, we demonstrated that Y501 in mutated RBD can be well coordinated by Y41 and K353 in hACE2 through hydrophobic interactions, increasing the overall binding affinity between RBD and hACE2 by about 0.81 kcal/mol..." Luan et al.,

Molecular Modeling of Y501 to ACE2 receptor

Y501 binding to ACE2

Above from Luan et al. shows increased binding with Y501 mutation to ACE2 receptor

Images above taken from Jsmol (below) from zooming into N501 amino acid, left Asparagine, right image the mutated Tyrosine amino acid. As shown above the mutation to Tyrosine results in a tighter association between the spike protein and ACE2 receptor

PDB:7DF4
-------------->spin on -------->- spin off
->zoom in to N501:B -------->- zoom out

To Rotate the Molecule--->Left Click and Drag
To Zoom-->>Left Click + hold Shift button and Drag Vertically
To see amino acid and atom number hold cursor over atom
Jmol Menu --->>Right-Click

PDB: 6MOJ
-------------->spin on -------->- spin off
->zoom in to Y501:E -------->- zoom out

To Rotate the Molecule--->Left Click and Drag
To Zoom-->>Left Click + hold Shift button and Drag Vertically
To see amino acid and atom number hold cursor over atom
Jmol Menu --->>Right-Click

Note on Y501:E pdb file used for Jsmol above: The Y501 mutation is shown as created using Swiss-PDB software. No further minimazations or MD were performed. Recent Note: --Public Health England (PHE) confirmed to The BMJ that they have now identified 11 cases of the UK B1.1.7 variant carrying the E484K mutation around the Bristol area and 40 cases of the original SARS-C0V-2 virus carrying the same E484K mutation in the Liverpool area. Public health officials are carrying out enhanced contact tracing, additional laboratory analysis, and testing in these areas. The variant is noted as B.1.525.