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SHIVER

SARS CoV-2 Historically Identified Variants in Epitope Regions

Last update: Dec 6, 2022

Dates of current data

Variants   Strategy   Reference

Variants: Delta and Omicron Variants
Strategy: Take turns
Reference strain: Wuhan reference
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

 111111111112222222233333333444444444444444455666
1444445555554445555534567777001444455677889900578
9456790236783451236796681356587045602078460815591 Name                    LPM    GPM    GSM  GSM/GPM [Mutations] (Lineage)
TYYHKNKWMEFRALHPGDSGGRKLSSSTDRKNKVGNLNSTEFFQNYHNP 1-Initial                 1      1      1   100.0% [] 
I...................D...FPFANSNK....R.NKAV.RYHYKH 2-North-America-1      4283  12729   7738    60.8% [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)
I...................DT..FPFANSNK....R.NKAV.RYHYKH 3-Europe-1             4128   9329   6192    66.4% [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,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.4andBA.5)
I...................DT..FPFANSNKT...RKNKAV.RYHYKH 4-Asia-1                770   9684   8061    83.2% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,G339D,R346T,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,K444T,L452R,N460K,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.4andBA.5)
I-..................D...FPFANSNKT...RKNKAV.RYHYKH 5-United-Kingdom-1      354   1973   1635    82.9% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,Y144-,V213G,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,K444T,L452R,N460K,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.4andBA.5)
I...E..R..L........SHT..FPFANSNK..S.RKNKAI.RYHYKH 6-Oceania-1             457    482    448    92.9% [T19I,L24-,P25-,P26-,A27S,G142D,K147E,W152R,F157L,I210V,V213G,G257S,G339H,R346T,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,G446S,L452R,N460K,S477N,T478K,E484A,F486I,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] 
I...................DT..FPFAN.NKT...RKNKAV.RYHYKH 7-South-America-1        43    120     95    79.2% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,G339D,R346T,S371F,S373P,S375F,T376A,D405N,K417N,N440K,K444T,L452R,N460K,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] 
I.Q-............V...HT.IFPFANSNK.PS..KNKASSRYHYKH 8-Africa-1                6   1077    789    73.3% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y145Q,H146-,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,V445P,G446S,N460K,S477N,T478K,E484A,F486S,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] 
I...................D...FPFANSNKT...RKNKAV.RYHYKH 9-North-America-2      3573   5405   3669    67.9% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,K444T,L452R,N460K,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.4andBA.5)
I-..................DT..FPFANSNKT...RKNKAV.RYHYKH 10-Europe-2            1294   2038   1771    86.9% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,Y144-,V213G,G339D,R346T,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,K444T,L452R,N460K,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.4andBA.5)
I...................D...FPFAN.NK....R.NKAV.RYHYKH 11-Asia-2               387    419    210    50.1% [T19I,L24-,P25-,P26-,A27S,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,K417N,N440K,L452R,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] 
I...E..R..L........SHTT.FPFANSNK..S..KNKA.SRYHYKH 12-United-Kingdom-2     288   1777   1424    80.1% [T19I,L24-,P25-,P26-,A27S,G142D,K147E,W152R,F157L,I210V,V213G,G257S,G339H,R346T,K356T,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,G446S,N460K,S477N,T478K,E484A,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] 
I...E..R..L........SHT..FPFANSNK..S..KNKAPSRYHYKH 13-Oceania-2            372    408    377    92.4% [T19I,L24-,P25-,P26-,A27S,G142D,K147E,W152R,F157L,I210V,V213G,G257S,G339H,R346T,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,G446S,N460K,S477N,T478K,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] 
I...................D...FPFAN.NKT...RKNKAV.RYHYKH 14-South-America-2       18     51     38    74.5% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,K417N,N440K,K444T,L452R,N460K,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] 
I-..................DT..FPFANSNK....R.NKAV.RYHYKH 15-Africa-2               5    428    302    70.6% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,Y144-,V213G,G339D,R346T,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)
I...................D...FPFANSNK...DR.NKAV.RYHYKH 16-North-America-3      253    799    517    64.7% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,N450D,L452R,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.4andBA.5)
I...................DI..FPFANSNK....R.NKAV.RYHYKH 17-Europe-3             304    450    351    78.0% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,G339D,R346I,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)
I-..................D...FPFANSNK....R.NKAV.RYHYKH 18-Asia-3                99    475    381    80.2% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,Y144-,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)
I...E..R..L........SHT..FPFANSNKT.S.RKNKAS.RYHYKH 19-United-Kingdom-3     145    388    269    69.3% [T19I,L24-,P25-,P26-,A27S,G142D,K147E,W152R,F157L,I210V,V213G,G257S,G339H,R346T,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,K444T,G446S,L452R,N460K,S477N,T478K,E484A,F486S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] 
I...E..R..L........SHT..FPFANSNK..S..KNKAS.RYHYKH 20-Oceania-3             93    424    147    34.7% [T19I,L24-,P25-,P26-,A27S,G142D,K147E,W152R,F157L,I210V,V213G,G257S,G339H,R346T,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,G446S,N460K,S477N,T478K,E484A,F486S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] 
I.Q-.............G..HT.IFPFAN.NK.PS..KNKASSRYHYKH 21-South-America-3       18     18     14    77.8% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y145Q,H146-,Q183E,V213E,D253G,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,K417N,N440K,V445P,G446S,N460K,S477N,T478K,E484A,F486S,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] 
I..............L....DT..FPFANSNKT...RKNKAV.RYHYKH 22-Africa-3               4     67     42    62.7% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,P251L,G339D,R346T,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,K444T,L452R,N460K,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.4andBA.5)
I...................DS..FPFANSNK....R.NKAV.RYHYKH 23-North-America-4      223    469    343    73.1% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,G339D,R346S,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)
I...--..............D...FPFANSNK....R.NKAV.RYHYKH 24-Europe-4             223    225    207    92.0% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,K147-,N149-,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,P1162S] (Omicron_BA.4andBA.5)
I.......T.....N....DD...FPFANSNKR..DMKNKR..RYHYKH 25-Asia-4                58    391    301    77.0% [T19I,L24-,P25-,P26-,A27S,G142D,M153T,N164K,V213G,H245N,G257D,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,K444R,N450D,L452M,N460K,S477N,T478K,E484R,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] 
I................G..DT..FPFANSNKT...RKNKAV.RYHYKH 26-United-Kingdom-4      51     98     90    91.8% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,D253G,G339D,R346T,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,K444T,L452R,N460K,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.4andBA.5)
I-.......G----....L.....FPFANSNK..S.M.NKAP.RYHYKH 27-Oceania-4             56     64     59    92.2% [T19I,P25S,G142D,Y144-,E156G,F157-,R158-,P209L,L212S,D215H,A222V,A243-,L244-,S256L,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,G446S,L452M,S477N,T478K,E484A,F486P,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N703I,N764K,D796Y,Q954H,N969K] 
I...................D...FPFAN.NKN...RKNKAV.RYHYKH 28-South-America-4       13     13      7    53.8% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,K417N,N440K,K444N,L452R,N460K,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] 
I.....E.............D...FPFANSNKN...RKNKAV.RYHYKH 29-Africa-4               3    172    112    65.1% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,K150E,V213G,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,K444N,L452R,N460K,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.4andBA.5)

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 61475 sequences.

                Continent Name Coverage

                     Global T-1    0.0000
              North-America T-1    0.0000
Europe-minus-United-Kingdom T-1    0.0000
                       Asia T-1    0.0000
             United-Kingdom T-1    0.0002
                    Oceania T-1    0.0000
              South-America T-1    0.0000
                     Africa T-1    0.0000

                     Global T-8    0.5758
              North-America T-8    0.5631
Europe-minus-United-Kingdom T-8    0.5856
                       Asia T-8    0.6666
             United-Kingdom T-8    0.5155
                    Oceania T-8    0.4774
              South-America T-8    0.3597
                     Africa T-8    0.7368

                     Global T-15   0.7470
              North-America T-15   0.7642
Europe-minus-United-Kingdom T-15   0.7239
                       Asia T-15   0.7913
             United-Kingdom T-15   0.7281
                    Oceania T-15   0.7216
              South-America T-15   0.4768
                     Africa T-15   0.8158

                     Global T-22   0.7896
              North-America T-22   0.7969
Europe-minus-United-Kingdom T-22   0.7727
                       Asia T-22   0.8226
             United-Kingdom T-22   0.7922
                    Oceania T-22   0.7847
              South-America T-22   0.5313
                     Africa T-22   0.8509

                     Global T-29   0.8129
              North-America T-29   0.8127
Europe-minus-United-Kingdom T-29   0.8048
                       Asia T-29   0.8340
             United-Kingdom T-29   0.8167
                    Oceania T-29   0.8240
              South-America T-29   0.5695
                     Africa T-29   0.9035

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 2022-11-06 to 2022-12-04. The number of sequences, broken out by continent is: Total: 61475, North-America: 21773, Europe-minus-United-Kingdom: 21296, Asia: 9109, United-Kingdom: 4413, Oceania: 4403, South-America: 367, Africa: 114. 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: Mon Aug 1 14:33 2022



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