'New Variant' Covid 19 -
Changes in the
SARS-CoV-2 spike protein
caused by mutations
As time passes, a number of changes in the amino acid sequence in the spike protein have been recorded.
And then there are some other differences reported in the virus from mink, as reported from Denmark and the Netherlands.
These have been described as mutants, new variants and simply new strains. There is concern about their infectivity and the possibility that they may be less susceptible to control by vaccines which are just becoming available.
Attention is focussed on antibodies to the spike protein as well as the action of T-cells. Groups of mutations have been used to describe and monitor the movement of the virus through populations, and geographical areas.
"Cluster 5" is a mutated variant of the SARS-CoV-2 virus, discovered in Northern Jutland, Denmark. It is believed to have been spread from minks to humans via mink farms.
Y453F, I692V, M1229I as well as two amino acid deletions H69del/V70del.
The first three are substitutions, and the deletion of 6 bases from 21765-21770 caused the loss of two amino acids from the polypeptide chain.
Cluster 5 Substitutions (and base code changes
- using the flexible base notation for triplet degeneracy)
is a substitution of phenylalanine (F) for tyrosine (Y) at position 453
[base code switched from UA
Y to UU
is a substitution of valine (V) for isoleucine (I) at position 692
[base code switched from A
UY to GUY
is a substitution of isoleucine (I) for methionine (M) at position 1229
[base code switched from AUR
- a transversion]
Spike deletion 21765-21770
(Partial) Base and amino acid sequence
A comparison of sections of (DNA) base sequences between reference sequence Wuhan-Hu-1 (at the top, in blue) and deletion 21765-21770 (in green).
The loss of 6 bases gives a triplet of ATC (bases 21764-21771-21772 in 'old numbers') still coding for an isoleucine ('same amino acid'), so the chain is simply shortened by 2 amino acids.
What are the two lost amino acids?
> H histidine
> V valine
I have taken the liberty of annotating base sequence data and amino acid listings
to show the effects of that deletion.
- Just look for lines I have inserted between the original data!
The D614G mutation
is an allele causing a modification of the virus' surface spike protein, which has become increasingly common. This notation means that the 614th amino acid in its polypeptide chain is altered from being aspartate - aspartic acid - (one-letter amino acid code D) to glycine (G). This is likely to be the result of a change (A to G) in the middle base of a codon in the viral RNA. It is said that this mutation appears to have greater transmissibility in humans rather than greater pathogenicity.
The BBC states that a strain A222V
spread across Europe and was linked to summer holidays in Spain.
What is the change in amino acid, and the base sequence? (Use the table above)
Amino acid 222 changed from > alanine
to > valine
, triplet changed from > GCN
to > GUN
The most recent version, and a cause of concern because of its apparently greater (70% ?) transmissibility, includes a number of mutations known from other parts of the world.
- N501Y (substitution of tyrosine for asparagine at 501 - triplet change AAY to UAY) codes for changes in one of six key contact residues within the receptor-binding domain (RBD) of the spike protein.
It has been identified as increasing binding affinity to the target protein ACE2 in lungs.
- The spike deletion 69-70del - See Spike deletion 21765-21770 above - may make the virus more resistant to the human immune response. It has also occurred a number of times in association with other RBD changes.
- Mutation P681H (substitution of histidine for proline at 681 - triplet change CCN to CAY) is immediately adjacent to the furin cleavage site, which enables the virus to easily enter into the host cell for infection, thus efficiently aiding its spread throughout the human population.