SHIVER
SARS CoV-2 Historically Identified Variants in Epitope Regions
Variants: Delta and Omicron Variants
Strategy: Take turns
Reference strain: Wuhan reference
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.
Questions or comments? Contact us at seq-info@lanl.gov.
