COVID-19 Viral Genome Analysis Pipeline COVID-19 Viral Genome Analysis Pipeline home COVID-19 Viral Genome Analysis Pipeline home
COVID-19 Viral Genome Analysis Pipeline
Enabled by data from   gisaid-logo


SHIVER

SARS CoV-2 Historically Identified Variants in Epitope Regions

Last update: Aug 9, 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

 11111222233333344444444444444556666
144555455534777700144456778899005778
947237857996135658704620784638155591 Name                    LPM    GPM    GSM  GSM/GPM [Mutations] (Lineage)
TYKWMFYSGTGRSSSTDRKNKGLNSTEFQQNYHQNP 1-Initial                 3      3      0     0.0% [] 
I.........D.FPFANSNK..R.NKAV.RYHY.KH 2-North-America-1     44773  92707  61398    66.2% [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)
I.........DTFPFANSNK..R.NKAV.RYHY.KH 3-Europe-1              578   3267   2171    66.5% [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..R.NKAV.RYHY.KH 4-United-Kingdom-1      159    740    528    71.4% [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.........D.FPFANSNK....NKA.RRYHY.KH 5-Asia-1                477   1193    599    50.2% [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.FPFANSNK..Q.NKA.RRYHY.KH 6-Oceania-1              51   4575   3278    71.7% [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.FPFANSN...R.NKAV.RYHY.KH 7-South-America-1       428   1588    941    59.3% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,L452R,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] 
I.........DSFPFANSNK..R.NKAV.RYHY.KH 8-Africa-1                6    251    115    45.8% [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,N658S,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.4andBA.5)
I.........D.FPFAN.......NKAV.RYHY.KH 9-North-America-2       130    131     70    53.4% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] 
I.........D.FPFAN.NK..R.NKAV.RYHY.KH 10-Europe-2             317    676    436    64.5% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,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........AD.FPFANSNK..R.NKAV.RYHY.KH 11-United-Kingdom-2     102    258    203    78.7% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,T259A,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.........D.FPFANSTK....NKA.RRYHY.KH 12-Asia-2               132    323    271    83.9% [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.FPF.NSNK..R.NKAV.RYHY.KH 13-Oceania-2             32     32     23    71.9% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,G339D,S371F,S373P,S375F,D405N,R408S,K417N,N440K,L452R,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] 
I.........D.FPFANSN...Q.NKA.RRYHY.KH 14-South-America-2       12     53     33    62.3% [T19I,L24-,P25-,P26-,A27S,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,L452Q,S477N,T478K,E484A,Q493R,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,S704L,N764K,D796Y,Q954H,N969K] 
I.........DTFPFANSN...R.NKAV.RYHY.KH 15-Africa-2               3     46     28    60.9% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,G339D,R346T,S371F,S373P,S375F,T376A,D405N,R408S,K417N,L452R,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N658S,N679K,P681H,N764K,D796Y,Q954H,N969K] 
I...I.....D.FPFANSNK..R.NKAV.RYHY.KH 16-North-America-3      116    218    116    53.2% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,M153I,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)
..........D.FPFANSNK..R.NKAV.RYHY.KH 17-Europe-3              78    146    116    79.5% [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] 
I......F..D.FPFANSNK..R.NKAV.RYHY.KH 18-United-Kingdom-3      58    227    137    60.4% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,S255F,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.....N...DTFPFANSNK....NKA.RRYHY.KH 19-Asia-3               121    258    208    80.6% [T19I,L24-,P25-,P26-,A27S,G142D,V213G,Y248N,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.FPFANSNK..R.NKAV.RYHYLKH 20-Oceania-3             19     23     18    78.3% [V3G,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,Q675L,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.4andBA.5)
I.........D.FPFANSN.....NKA.RRYHY.KH 21-South-America-3       11     30      8    26.7% [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.FPFANSNKT.R.NKAV.RYHY.KH 22-Africa-3               2    108     89    82.4% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,K444T,L452R,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.4andBA.5)
I.........D.FPFANSNK..M.NKA.RRYHY.KH 23-North-America-4      108    256    140    54.7% [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.........DIFPFANSNK..R.NKAV.RYHY.KH 24-Europe-4              76    169    110    65.1% [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..L......DTFPFANSNK..R.NKAV.RYHY.KH 25-United-Kingdom-4      40     49     41    83.7% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,W152L,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.ER.L..S.H.FPFANSNK.S.KNKA..RYHY.KH 26-Asia-4                85    162     78    48.1% [T19I,L24-,P25-,P26-,A27S,G142D,K147E,W152R,F157L,I210V,V213G,G257S,G339H,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,G446S,N460K,S477N,T478K,E484A,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] 
I.........DTFPFANSNK....NKA.RRYHY.KH 27-Oceania-4             15     42     14    33.3% [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.FPFANSN...M.NKA.RRYHY.KH 28-South-America-4       10     14     11    78.6% [T19I,L24-,P25-,P26-,A27S,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,L452M,S477N,T478K,E484A,Q493R,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.2+L452M)
I.........D.FPFANSNK..R.NKA..RYHY.KH 29-Africa-4               1     12      5    41.7% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,L452R,S477N,T478K,E484A,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] 

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 113720 sequences.

                Continent Name Coverage

                     Global T-1    0.0000
              North-America T-1    0.0000
Europe-minus-United-Kingdom T-1    0.0000
             United-Kingdom T-1    0.0000
                       Asia T-1    0.0003
                    Oceania T-1    0.0000
              South-America T-1    0.0000
                     Africa T-1    0.0000

                     Global T-8    0.9174
              North-America T-8    0.9291
Europe-minus-United-Kingdom T-8    0.9158
             United-Kingdom T-8    0.9326
                       Asia T-8    0.8533
                    Oceania T-8    0.9143
              South-America T-8    0.8380
                     Africa T-8    0.8980

                     Global T-15   0.9307
              North-America T-15   0.9376
Europe-minus-United-Kingdom T-15   0.9310
             United-Kingdom T-15   0.9408
                       Asia T-15   0.8878
                    Oceania T-15   0.9306
              South-America T-15   0.8932
                     Africa T-15   0.9235

                     Global T-22   0.9396
              North-America T-22   0.9440
Europe-minus-United-Kingdom T-22   0.9400
             United-Kingdom T-22   0.9493
                       Asia T-22   0.9068
                    Oceania T-22   0.9452
              South-America T-22   0.9081
                     Africa T-22   0.9388

                     Global T-29   0.9458
              North-America T-29   0.9479
Europe-minus-United-Kingdom T-29   0.9455
             United-Kingdom T-29   0.9553
                       Asia T-29   0.9219
                    Oceania T-29   0.9602
              South-America T-29   0.9308
                     Africa T-29   0.9541

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 2022-07-10 to 2022-08-02. The number of sequences, broken out by continent is: Total: 113720, North-America: 55999, Europe-minus-United-Kingdom: 27451, United-Kingdom: 14545, Asia: 11447, Oceania: 2940, South-America: 1142, Africa: 196. 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



GISAID data provided on this website is subject to GISAID's Terms and Conditions
Questions or comments? Contact us at seq-info@lanl.gov.

 
Operated by Triad National Security, LLC for the U.S. Department of Energy's National Nuclear Security Administration
© Copyright Triad National Security, LLC. All Rights Reserved | Disclaimer/Privacy

Dept of Health & Human Services Los Alamos National Institutes of Health