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1

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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