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
1111111122222222333333333444444444444444444445555666 14444555544555556334567777000144445556777888990012578 94567267834123671596681356358704562560578146081511591 Name LPM GPM GSM GSM/GPM [Mutations] (Lineage) TYYHKWEFRAL-GDSGGLGRKLSSSTRDRKNKVGLLFNASTNEFFQNYVPHNP 1-Initial 0 0 0 0.0% [] I-.Q........V.....HT.IFPFA.NSNK.PS..LK.NK.APSRYH..YKH 2-North-America-1 1968 3831 2140 55.9% [T19I,L24-,P25-,P26-,A27S,Q52H,V83A,G142D,Y144-,H146Q,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,V445P,G446S,F456L,N460K,S477N,T478K,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I-.Q.........G....HT.IFPFA.NSNK.PS...K.NR.APSRYH.SYKH 3-Europe-1 276 633 143 22.6% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y144-,H146Q,Q183E,N185I,F186-,V213E,D253G,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,V445P,G446S,N460K,S477N,T478R,E484A,F486P,F490S,Q498R,N501Y,Y505H,P521S,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I-.Q........V.....HT.IFPFA.NSNK.PS.FLK.NK.APSRYH..YKH 4-Asia-1 289 775 292 37.7% [T19I,L24-,P25-,P26-,A27S,Q52H,V83A,G142D,Y144-,H146Q,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,V445P,G446S,L455F,F456L,N460K,S477N,T478K,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I-.Q........V.....HT.IFPFA.NSNK.PS...K.NR.APSRYH..YKH 5-United-Kingdom-1 196 1586 315 19.9% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y144-,H146Q,E180V,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,V445P,G446S,N460K,S477N,T478R,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I-....G----...L....S..FPFA.NSNK..SR....NK.AP.RYH..YKH 6-Oceania-1 50 55 31 56.4% [T19I,P25S,G142D,Y144-,E156G,F157-,R158-,P209L,L212S,D215H,A222V,A243-,L244-,S256L,R346S,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,G446S,L452R,S477N,T478K,E484A,F486P,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N703I,N764K,D796Y,Q954H,N969K] I-.Q........V.....HT.IFPFA.N.NK.PS..LK.NK.APSRYH..YKH 7-South-America-1 5 58 21 36.2% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y144-,H146Q,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,K417N,N440K,V445P,G446S,F456L,N460K,S477N,T478K,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I-.Q........V.....HT.IFPFA.NSNK.PS...K.NR.APSRYH.TYKH 8-Africa-1 4 403 262 65.0% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y144-,H146Q,E180V,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,V445P,G446S,N460K,S477N,T478R,E484A,F486P,F490S,Q498R,N501Y,Y505H,P521T,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I-.Q........V.....HT.IFPFA.NSNK.PS..LK.NR.APSRYH..YKH 9-North-America-2 1205 1656 620 37.4% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y144-,H146Q,E180V,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,V445P,G446S,F456L,N460K,S477N,T478R,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I...ER.L.......S..HT..FPFA.NSNKT.SRFLK.NK.AS.RYH..YKH 10-Europe-2 135 273 162 59.3% [T19I,L24-,P25-,P26-,A27S,G142D,K147E,W152R,F157L,N185D,I210V,V213G,G257S,G339H,R346T,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,K444T,G446S,L452R,L455F,F456L,N460K,S477N,T478K,E484A,F486S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,L858I,Q954H,N969K] I-.Q........V.....HT.IFPFA.NSNK.PS...K.NK.APSRYH..YKH 11-Asia-2 173 650 98 15.1% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y144-,H146Q,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,V445P,G446S,N460K,S477N,T478K,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I-.Q.......V.-....HT.IFPFA.NSNK.PS..LK.NK.APSRYH..YKH 12-United-Kingdom-2 64 127 92 72.4% [T19I,L24-,P25-,P26-,A27S,Q52H,V83A,G142D,Y144-,H146Q,Q183E,V213E,+251V,D253-,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,V445P,G446S,F456L,N460K,S477N,T478K,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I-.Q........V.....HT.IFPFA.NSNK.PS.FLK.NR.APSRYH..YKH 13-Oceania-2 15 87 68 78.2% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y144-,H146Q,E180V,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,V445P,G446S,L455F,F456L,N460K,S477N,T478R,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I-.Q...L....V.....HTTIFPFA.NSNK.PS...K.NK.APSRYH..YKH 14-South-America-2 3 4 2 50.0% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y144-,H146Q,F157L,Q183E,V213E,G252V,G339H,R346T,K356T,L368I,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,V445P,G446S,N460K,S477N,T478K,E484A,F486P,F490S,Q498R,N501Y,Y505H,T572I,D614G,H655Y,N679K,P681H,N764K,Q954H,N969K] I-.Q........V....SHT.IFPFAKNSNK.PS...K.NR.APSRYH..YKH 15-Africa-2 2 30 16 53.3% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y144-,H146Q,Q183E,V213E,G252V,L335S,G339H,R346T,L368I,S371F,S373P,S375F,T376A,R403K,D405N,R408S,K417N,N440K,V445P,G446S,N460K,S477N,T478R,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I-.Q.........G....HT.IFPFA.NSNK.PS...K.NK.APSRYH.SYKH 16-North-America-3 353 500 196 39.2% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y144-,H146Q,K182N,Q183E,V213E,D253G,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,V445P,G446S,N460K,S477N,T478K,E484A,F486P,F490S,Q498R,N501Y,Y505H,P521S,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I.QN-.......V.....HT.IFPFA.NSNK.PS...K.NR.APSRYH.SYKH 17-Europe-3 74 198 143 72.2% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y145Q,H146N,K147-,E180V,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,V445P,G446S,N460K,S477N,T478R,E484A,F486P,F490S,Q498R,N501Y,Y505H,P521S,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I...ER.L.......S..HT..FPFA.NSNKT.SR..K.NK.AS.RYH..YKH 18-Asia-3 38 60 21 35.0% [T19I,L24-,P25-,P26-,A27S,G142D,K147E,W152R,F157L,I210V,V213G,D215G,G257S,G339H,R346T,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,K444T,G446S,L452R,N460K,S477N,T478K,E484A,F486S,Q498R,N501Y,Y505H,Q613H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K,E1111Q] I-.Q........V.....HT.IFPFA.NSNK.PS.FLK.NK.APSRYHI.YKH 19-United-Kingdom-3 23 149 87 58.4% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y144-,H146Q,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,V445P,G446S,L455F,F456L,N460K,S477N,T478K,E484A,F486P,F490S,Q498R,N501Y,Y505H,V511I,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I-.Q...L....V.....HT.IFPFA.NSNK.PS..LK.NK.APSRYH..YKH 20-Oceania-3 12 233 161 69.1% [T19I,L24-,P25-,P26-,A27S,Q52H,V83A,G142D,Y144-,H146Q,F157L,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,V445P,G446S,F456L,N460K,S477N,T478K,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I-.Q........V.....H..IFPFA.NSNK.PS..LK.NK.APSRYH..YKH 21-South-America-3 2 3 3 100.0% [T19I,L24-,P25-,P26-,A27S,Q52H,V83A,G142D,Y144-,H146Q,Q183E,V213E,G252V,G339H,L368I,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,V445P,G446S,F456L,N460K,S477N,T478K,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I..QER.L.......S..HT.IFPFAKNSNKTPSR..K.NR.APSRYH..YKH 22-Africa-3 1 1 1 100.0% [T19I,L24-,P25-,P26-,A27S,V36I,V83A,G142D,H146Q,K147E,W152R,F157L,G181E,Q183E,I210V,V213G,G257S,G339H,R346T,L368I,S371F,S373P,S375F,T376A,R403K,D405N,R408S,K417N,N440K,K444T,V445P,G446S,L452R,N460K,S477N,T478R,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K,G1219V] I-.Q...L....V.....HT.IFPFA.NSNK.PSR.LK.NK.APSRYH..YKH 23-North-America-4 304 342 282 82.5% [T19I,L24-,P25-,P26-,A27S,Q52H,V83A,G142D,Y144-,H146Q,F157L,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,V445P,G446S,L452R,F456L,N460K,S477N,T478K,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I-.Q........V.....HT.IFPFA.NSNK.PS.FLKVNK.APSRYH..YKH 24-Europe-4 70 137 99 72.3% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y144-,H146Q,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,V445P,G446S,L455F,F456L,N460K,A475V,S477N,T478K,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I-.K........V.....HT.IFPFA.NSNK.PS..LK.NK.APSRYH..YKH 25-Asia-4 16 145 81 55.9% [T19I,L24-,P25-,P26-,A27S,Q52H,V83A,G142D,Y144-,H146K,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,V445P,G446S,F456L,N460K,S477N,T478K,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I-.Q........V.....HT.IFPFA.NSNK.PS..LK.NKKAPPRYH..YKR 26-United-Kingdom-4 14 22 17 77.3% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y144-,H146Q,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,V445P,G446S,F456L,N460K,S477N,T478K,N481K,E484A,F486P,F490P,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681R,A701V,N764K,D796Y,Q954H,N969K] I-....G----...L....S..FPFA.NSNK.ASR....NK.AP.RYH..YKH 27-Oceania-4 9 9 6 66.7% [T19I,P25S,G142D,Y144-,E156G,F157-,R158-,P209L,L212S,D215H,A222V,A243-,L244-,S256L,R346S,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,V445A,G446S,L452R,S477N,T478K,E484A,F486P,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N703I,N764K,D796Y,Q954H,N969K] I-.Q........V.....HT.IFPFA.N.NK.PS..LK.NR.APSRYH..YKH 28-South-America-4 2 14 5 35.7% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y144-,H146Q,E180V,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,K417N,N440K,V445P,G446S,F456L,N460K,S477N,T478R,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I-.K........V...VSHT.IFPFAKNSNK.PS...K.NR.APSRYH..YKH 29-Africa-4 1 1 1 100.0% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y144-,H146K,Q183E,V213E,G252V,G261V,L335S,G339H,R346T,L368I,S371F,S373P,S375F,T376A,R403K,D405N,R408S,K417N,N440K,V445P,G446S,N460K,S477N,T478R,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K,I1227V]
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 14737 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 0.0000
Oceania T-1 0.0000
South-America T-1 0.0000
Africa T-1 0.0000
Global T-8 0.4981
North-America T-8 0.4760
Europe-minus-United-Kingdom T-8 0.5080
Asia T-8 0.5530
United-Kingdom T-8 0.5171
Oceania T-8 0.5045
South-America T-8 0.5455
Africa T-8 0.5758
Global T-15 0.6900
North-America T-15 0.6982
Europe-minus-United-Kingdom T-15 0.6671
Asia T-15 0.6787
United-Kingdom T-15 0.7265
Oceania T-15 0.6441
South-America T-15 0.6667
Africa T-15 0.6970
Global T-22 0.7676
North-America T-22 0.7833
Europe-minus-United-Kingdom T-22 0.7439
Asia T-22 0.7243
United-Kingdom T-22 0.8084
Oceania T-22 0.7297
South-America T-22 0.6970
Africa T-22 0.7576
Global T-29 0.8131
North-America T-29 0.8413
Europe-minus-United-Kingdom T-29 0.7827
Asia T-29 0.7392
United-Kingdom T-29 0.8426
Oceania T-29 0.7793
South-America T-29 0.7273
Africa T-29 0.8182
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 2023-08-26 to 2023-09-19. The number of sequences, broken out by continent is: Total: 14737, North-America: 7610, Europe-minus-United-Kingdom: 3581, Asia: 1821, United-Kingdom: 1404, Oceania: 222, South-America: 66, Africa: 33. 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.
