Coronavirus New Variant VUI–202012/01
A new variant
strain of SARS-CoV-2 that contains a series of mutations has
been described in the United Kingdom (UK) and become highly
prevalent in London and southeast England. Based on these
mutations, this variant strain has been predicted to
potentially be more rapidly transmissible than other
circulating strains of SARS-CoV-2. At this time, there is no
evidence that this variant causes more severe illness or
increased risk of death.
The new variant is
defined by 23 mutations: 13-non synonymous mutations, 4
deletions and 6 synonymous mutations. The non-synonymous
mutations include a series of spike protein mutations (Table
1). Other notable mutations include a stop codon in ORF8.
There are 6 synonymous mutations with 5 in ORF1ab (C913T,
C5986T, C14676T, C15279T, C16176T), and one in the M gene
(T26801C). This is an unusually large number of mutations in
a single cluster.
Gene |
Nucleotide |
Amino acid |
ORF1ab |
C3267T |
T1001I |
Spike |
C5388A |
A1708D |
T6954C |
I2230T |
11288-11296 deletion |
SGF 3675-3677 deletion |
21765-21770 deletion |
HV 69-70 deletion |
21991-21993 deletion |
Y144 deletion |
A23063T |
N501Y |
C23271A |
A570D |
C23604A |
P681H |
C23709T |
T716I |
Orf8 |
T24506G |
S982A |
G24914C |
D1118H |
C27972T |
Q27stop |
G28048T |
R52I |
A28111G |
Y73C |
N |
28280 GAT->CTA |
D3L |
C28977T |
S235F |
(Table 1)
The
spike deletion 69-70del has
also occurred a number of times in association with other
RBD changes.
Mutation
N501Y is one of six key contact residues within the
receptor-binding domain (RBD) and has been identified as
increasing binding affinity to human ACE2.
Mutation
P681H is immediately adjacent
to the furin cleavage site, a known location of biological
significance.
Transmissibility: It is highly likely
that N501Y affects the receptor binding affinity of the
spike protein and it is possible that this mutation alone or
in combination with the deletion at 69/70 in the N terminal
domain (NTD) is enhancing the transmissibility of the virus.
This is based on the position of the 501 residue in the
spike receptor binding domain and data showing that N501Y
increases spike interactions with human ACE2. N501Y is one
of a number of artificially generated RBD variants shown to
do this (others include Y453F and N439K). It should be noted
that this mutation is the only spike variant found to date
in mouse-adapted SARS-CoV2 and is also seen in ferret
infections.
Antigenicity: Position 501 is in the RBD, where
neutralising antibodies most frequently act, and therefore
it is possible that variants at this position affect the
efficacy of neutralisation of virus. Of several monoclonal
antibodies tested across different studies, one (LYCoV016)
showed decreased ability to neutralise SARS-CoV2 variants
with mutations at position 501. N501Y was not included.
There is currently no neutralisation data on N501Y available
from polyclonal sera from natural infection.
the sequence of
spike glycoprotein:
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