United States Q677P Mutation

Q677P substitution in Spike Protein

"... Independent genomic surveillance programs based in New Mexico and Louisiana contemporaneously detected the rapid rise of numerous clade 20G (lineage B.1.2) infections carrying a Q677P substitution in S. The variant was first detected in the US on October 23, yet between 01 Dec 2020 and 19 Jan 2021 it rose to represent 27.8% and 11.3% of all SARS-CoV-2 genomes sequenced from Louisiana and New Mexico, respectively. Q677P cases have been detected predominantly in the south central and southwest United States; as of 03 Feb 2021...

...We further provide phylogenetic analyses that identify six independent Q677H sub-lineages and one Q677P sub-lineage that all appear to have emerged within the United States. These variants were not detected until mid-August 2020, but as of 03 Feb 2021 already account for over 2,327 of the 102,462 genomes deposited to GISAID from the USA. Given the broad..."

source: Emergence in late 2020 of multiple lineages of SARS-CoV-2 Spike protein variants affecting amino acid position 677

..Modeled structure of variants---

The S1/S2 cleavage site contains the multibasic cleavage site and is found in a disordered region within Spike (S). Hodcroft et al., used SWISS MODEL to model this inherently flexible region and spotlight the Q677P residue (figure below)

Above image: from Hodcroft et al., Structure of SARS-CoV-2 Spike protein denoting location of Q677P within a disordered loop adjacent to the polybasic (furin) cleavage site. Structure was modeled from PDB: 7BBH using SWISS-MODEL and visualized using PyMol. bStructure of SARS-CoV-2 Spike protein denoting location of Q677P within a disordered loop adjacent to the polybasic (furin) cleavage site. Structure was modeled from PDB: 7BBH using SWISS-MODEL and visualized using PyMol.

"...Although the Q677P position is outside the furin binding pocket Hodcroft et al., speculate that the presence of a proline at this site may introduce a favorable kink that promotes the dynamic, conformational changes necessary for cleavage at the S1/S2 junction, which is governed not only by furin-like activities, but also by trypsin-like proteases and cathepsins..." source Hodcroft et al.,

Two variants have merged into heavily mutated coronavirus The UK and California variants of coronavirus appear to have combined into a heavily mutated hybrid, sparking concern that we may be entering a new phase of the covid-19 pandemic

"...The hybrid virus is the result of recombination of the highly transmissible B.1.1.7 variant discovered in the UK and the B.1.429 variant that originated in California and which may be responsible for a recent wave of cases in Los Angeles because it carries a mutation making it resistant to some antibodies. ..."

BELOW: Jsmol for pdb: 7jji -- Zoom in on right file to see the disordered region of Q677P. Amino acids #678-689 not shown. Hodcroft image above models that region.

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