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SHIVER

SARS CoV-2 Historically Identified Variants in Epitope Regions

Last update: May 21, 2022

Dates of current data

Variants   Strategy  

Variants: Delta and Omicron Variants
Strategy: Take turns
Early 2021 Variants color key
Delta Variants color key
Delta Omicron Variants color key

SHIVER: SARS CoV-2 Historically Identified Variants in Epitope Regions

SHIVER identifies variant forms of the SARS CoV-2 virus with a focus on the NTD and RBD neutralizing antibody epitope regions of the Spike protein, as well as sites related to furin cleavage; the forms are chosen to maximize coverage globally and/or on separate continents[*], depending on which of several strategies is employed.

In the Table of Variants, below, the first column is the pattern at sites where differences occur, relative to initial (Wuhan) sequence, with site numbers read down vertically.

Table of Variants


LPM = Local Pattern Matches = # of seqs in continent that match over epitope region GPM = Global Pattern Matches = # of seqs in world that match over epitope region
GSM = Global Sequence Matches = # of seqs in world that match over whole Spike protein

 1111223333333344444444444444455666
14445453455777700144457788999900578
93457859667135658706927846346815591 Name                    LPM    GPM    GSM  GSM/GPM [Mutations] (Lineage)
TVYYFYSGRKRSSSTDRKNGYLSTEFQSGQNYHNP 1-Initial                 2      2      0     0.0% [] 
I......D...FPFANSNK...NKA.R..RYHYKH 2-North-America-1     21958  77737  58927    75.8% [T19I,L24-,P25-,P26-,A27S,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,S477N,T478K,E484A,Q493R,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.2)
I......D...FPFANSN....NKA.R..RYHYKH 3-Europe-1             1397   1832   1260    68.8% [T19I,L24-,P25-,P26-,A27S,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,S477N,T478K,E484A,Q493R,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.2)
I......D...FPFANSTK...NKA.R..RYHYKH 4-United-Kingdom-1      682   1048    926    88.4% [T19I,L24-,P25-,P26-,A27S,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417T,N440K,S477N,T478K,E484A,Q493R,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.2+K417T)
I......D...FPFAN.NK...NKA.R..RYHYKH 5-Asia-1                185    486    378    77.8% [T19I,L24-,P25-,P26-,A27S,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,K417N,N440K,S477N,T478K,E484A,Q493R,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] 
.---...D...LPF...NKS..NKA.R.SRYHYKH 6-Oceania-1              33    108     52    48.1% [A67V,H69-,V70-,T95I,G142D,V143-,Y144-,Y145-,N211-,L212I,+214EPE,G339D,S371L,S373P,S375F,K417N,N440K,G446S,S477N,T478K,E484A,Q493R,G496S,Q498R,N501Y,Y505H,T547K,D614G,H655Y,N679K,P681H,N764K,D796Y,N856K,Q954H,N969K,L981F] (Omicron_BA.1)
I......D...FPFANSNK..RNKAV...RYHYKH 7-Africa-1              413   1141    481    42.2% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,L452R,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.4andBA.5)
.---...DK..LPF...NKS..NKA.R.SRYHYKH 8-South-America-1        10    947    663    70.0% [A67V,H69-,V70-,T95I,G142D,V143-,Y144-,Y145-,N211-,L212I,+214EPE,G339D,R346K,S371L,S373P,S375F,K417N,N440K,G446S,S477N,T478K,E484A,Q493R,G496S,Q498R,N501Y,Y505H,T547K,D614G,H655Y,N679K,P681H,N764K,D796Y,N856K,Q954H,N969K,L981F] (Omicron_BA.1.1)
I......D...FPFANSNK..QNKA.R..RYHYKH 9-North-America-2     11144  11651   9829    84.4% [T19I,L24-,P25-,P26-,A27S,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,L452Q,S477N,T478K,E484A,Q493R,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,S704L,N764K,D796Y,Q954H,N969K] (Omicron_BA.2+L452Q+S704L_BA.2.12.1)
I......D...FPFANSNK..MNKA.R..RYHYKH 10-Europe-2             504    740    462    62.4% [T19I,L24-,P25-,P26-,A27S,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,L452M,S477N,T478K,E484A,Q493R,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.2+L452M)
I......D.R.FPFANSNK...NKA.R..RYHYKH 11-United-Kingdom-2     109    153    111    72.5% [T19I,L24-,P25-,P26-,A27S,G142D,V213G,G339D,K356R,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,S477N,T478K,E484A,Q493R,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.2)
.......D...FPFANSNK...NKA.R..RYHYKH 12-Asia-2                79    106     82    77.4% [L24-,P25-,P26-,A27S,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,S477N,T478K,E484A,Q493R,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] 
I......D..KFPFANSNK...NKA.R..RYHYKH 13-Oceania-2             21     50     23    46.0% [T19I,L24-,P25-,P26-,A27S,G142D,V213G,G339D,R357K,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,S477N,T478K,E484A,Q493R,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.2)
I...L..D...FPFANSNK..RNKAV...RYHYKH 14-Africa-2               7      7      6    85.7% [V3G,T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,F157L,V213G,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,L452R,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.4andBA.5)
.---...DK..LPF...N.S..NKA.R.SRYHYKH 15-South-America-2        4      5      1    20.0% [A67V,H69-,V70-,T95I,G142D,V143-,Y144-,Y145-,N211-,L212I,+214EPE,G339D,R346K,S371L,S373P,S375F,K417N,G446S,S477N,T478K,E484A,Q493R,G496S,Q498R,N501Y,Y505H,T547K,H655Y,N679K,P681H,N764K,D796Y,N856K,Q954H,N969K] 
I.....FD...FPFANSNK...NKA.R..RYHYKH 16-North-America-3      229    387    320    82.7% [T19I,L24-,P25-,P26-,A27S,G142D,V213G,S255F,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,S477N,T478K,E484A,Q493R,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.2)
I......D...FPFANSNK...NKA.R..RYHYK. 17-Europe-3             448    448    342    76.3% [T19I,L24-,P25-,P26-,A27S,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,S477N,T478K,E484A,Q493R,Q498R,N501Y,Y505H,D614G,H655Y,N679K,N764K,D796Y,Q954H,N969K] 
I...L..D...FPFANSNK...NKA.R..RYHYKH 18-United-Kingdom-3      82    212    176    83.0% [T19I,L24-,P25-,P26-,A27S,G142D,F157L,V213G,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,S477N,T478K,E484A,Q493R,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.2)
.......D...YPFANSNK...NKA.R..RYHYKH 19-Asia-3                68     68     63    92.6% [L24-,P25-,P26-,A27S,G142D,V213G,G339D,S371Y,S373P,S375F,T376A,D405N,R408S,K417N,N440K,S477N,T478K,E484A,Q493R,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K,E1202Q] 
.---...DK..LPF...NK...NKA.R.SRYHYKH 20-Oceania-3              5     14      7    50.0% [A67V,H69-,V70-,T95I,G142D,V143-,Y144-,Y145-,N211-,L212I,+214EPE,G339D,R346K,S371L,S373P,S375F,K417N,N440K,S477N,T478K,E484A,Q493R,G496S,Q498R,N501Y,Y505H,T547K,D614G,H655Y,N679K,P681H,N764K,D796Y,N856K,Q954H,N969K,L981F] (Omicron_BA.1.1)
I......D...FPFANSNK...NKA.RP.RYHYKH 21-Africa-3               3     52     37    71.2% [T19I,L24-,P25-,P26-,A27S,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,S477N,T478K,E484A,Q493R,S494P,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.2)
I......D....PFANSNK...NKA.R..RYHYKH 22-South-America-3        4     96     81    84.4% [T19I,L24-,P25-,P26-,A27S,G142D,V213G,G339D,S373P,S375F,T376A,D405N,R408S,K417N,N440K,S477N,T478K,E484A,Q493R,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] 
I....S.D...FPFANSNK...NKA.R..RYHYKH 23-North-America-4      190    306    248    81.0% [T19I,L24-,P25-,P26-,A27S,G142D,V213G,Y248S,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,S477N,T478K,E484A,Q493R,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.2)
I....H.D...FPFANSNK...NKA.R..RYHYKH 24-Europe-4             181    277    133    48.0% [T19I,L24-,P25-,P26-,A27S,G142D,V213G,Y248H,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,S477N,T478K,E484A,Q493R,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K,S1261Y] (Omicron_BA.2)
I......DT..FPFANSNK...NKA.R..RYHYKH 25-United-Kingdom-4      28    159    123    77.4% [T19I,L24-,P25-,P26-,A27S,G142D,V213G,G339D,R346T,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,S477N,T478K,E484A,Q493R,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.2)
I......D...YPFANSNK...NKA.R..RYHYKH 26-Asia-4                27    111     61    55.0% [T19I,L24-,P25-,P26-,A27S,G142D,V213G,G339D,S371Y,S373P,S375F,T376A,D405N,R408S,K417N,N440K,S477N,T478K,E484A,Q493R,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] 
I......D...FPFANSNK..RNKA.R..RYHYKH 27-Oceania-4              4    173    147    85.0% [T19I,L24-,P25-,P26-,A27S,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,L452R,S477N,T478K,E484A,Q493R,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] 
I......DT..FPFANSNK..RNKAV...RYHYKH 28-Africa-4               2      4      3    75.0% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,G339D,R346T,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,L452R,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N658S,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.4andBA.5)
I......D...FPFANSNK.N.NKA.R..RYHYKH 29-South-America-4        2     60     56    93.3% [T19I,L24-,P25-,P26-,A27S,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,Y449N,S477N,T478K,E484A,Q493R,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.2)

In the Table of Variants, above, the first variant in the input alignment is taken as the reference sequence, and is the ancestral Wuhan variant to ensure epitope regions are chosen appropriately. The alignment on the left shows the positions that define unique common forms that are searched using SHIVER. The positions numbers are written vertically. The amino acids in the top row are taken from is the ancestral Wuhan variant. The epitope regions in Spike that are explored for a focused search for the common Spike variants are defined at the end of this document. The epitope and furin cleavage regions in Spike that are featured are defined below.

The basic NTD supersite sites selected are for inclusion are based on:

Sites 14-20, 140-158, and 245-264: McCallum, M. et al. N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2. Cell 184:9 2332-2347.e16 (2021)

Site 13: Impacts signal peptide cleavage and NTDss antibodies. McCallum, M. et al. SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern. Science 373:648-654 (2021)

Sites 242-244: Impacts NTDss antibody potency SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma Wibmer, C. et al. Nature Med. 27(4): 622-625.

Toggling Sites: Site 18 is in the NTDss and toggles frequently between L and F, so we exclude it from the tallies of forms of the regions of interest as it splits the counts on otherwise distinctive forms. An analogous situation is a problem for site 142. Among Delta variants, every common variant within the Delta lineages includes both (the ancestral) G and D at site 142. This is because the ARTIC 3 primers can results in an erroneous call of the ancestral G at position 142. The G142D mutation is the common form, and this error is resolved by using the ARTIC 4 primers. By excluding both sites 18 and 142 from our NTDss definition, we group the forms of Spike that carry either form in our tallies.

Analysis of the ARTIC version 3 and version 4 SARS-CoV-2 primers and their impact on the detection of the G142D amino acid substitution in the spike protein. Davies et al. bioRxiv 10.1101/2021.09.27.461949 (2021)

Sites 330-521: the RBD region includes positions 330-521, based on a synthesis of the literature from early 2020.

Furin related sites: mutations that add positive charge to near the furin cleavage site can enhance Spike cleavage and infectivity. Also, the change at H655Y (Alba2021) has been shown to impact furin cleavage, and we include site 950 as it accompanies P681R in Delta and P681H in Mu, to variants that were particularly fast spreading, though Delta became prevalent. SARS-CoV-2 spike P681R mutation, a hallmark of the Delta variant, enhances viral fusogenicity and pathogenicity. Saito et al. bioRxiv 10.1101/2021.06.17.448820 (2021) SARS-CoV-2 variants of concern have acquired mutations associated with an increased spike cleavage. Alba et al. bioRxiv 10.1101/2021.08.05.455290 (2021)

Table of Coverages

In table below, T-n refers to a batch of the first n variants. Coverage is defined as fraction of sequences in the continent with an exact match (over the region NTDss-18-142+RBD+furin) to one of the first n variants. (Here, 'T' corresponds to the 'Taketurns' strategy.) The coverage table is based on 102367 sequences.

                Continent Name Coverage

                   Global T-1    0.0000
            North-America T-1    0.0001
Europe-minus-United-Kingdom T-1    0.0000
           United-Kingdom T-1    0.0000
                     Asia T-1    0.0000
                  Oceania T-1    0.0000
                   Africa T-1    0.0000
            South-America T-1    0.0000

                   Global T-8    0.8137
            North-America T-8    0.6364
Europe-minus-United-Kingdom T-8    0.8928
           United-Kingdom T-8    0.9471
                     Asia T-8    0.8469
                  Oceania T-8    0.9510
                   Africa T-8    0.9330
            South-America T-8    0.8456

                   Global T-15   0.9379
            North-America T-15   0.9443
Europe-minus-United-Kingdom T-15   0.9152
           United-Kingdom T-15   0.9626
                     Asia T-15   0.9019
                  Oceania T-15   0.9715
                   Africa T-15   0.9457
            South-America T-15   0.9128

                   Global T-22   0.9504
            North-America T-22   0.9526
Europe-minus-United-Kingdom T-22   0.9361
           United-Kingdom T-22   0.9687
                     Asia T-22   0.9239
                  Oceania T-22   0.9782
                   Africa T-22   0.9511
            South-America T-22   0.9463

                   Global T-29   0.9611
            North-America T-29   0.9596
Europe-minus-United-Kingdom T-29   0.9534
           United-Kingdom T-29   0.9760
                     Asia T-29   0.9360
                  Oceania T-29   0.9817
                   Africa T-29   0.9547
            South-America T-29   0.9597

This run uses the T=taketurns strategy for identifying further variants. Each continent, in turn, chooses the next variant, based on which is the most common variant in that continent that has not already been chosen. The order of the continents is based on number of samples available in those continents.

Sequence sample dates range from 2022-04-19 to 2022-05-16. The number of sequences, broken out by continent is: Total: 102367, North-America: 36655, Europe-minus-United-Kingdom: 34277, United-Kingdom: 24617, Asia: 3874, Oceania: 2243, Africa: 552, South-America: 149. The focus here is specifically on the epitope region: NTDss-18-142+RBD+furin Sites: 13-17,19,20,140,141,143-158,242-264,330-521,655,675,677,679,681,950

[*] Note that the UK is treated as a separate continent because so much of the sequencing has been from the UK.


 

last modified: Thu Apr 21 17:09 2022



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