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