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
11111112222223333333334444444444444444555666 144455554455553455677770011444456778899002578 946726783423679646813565807045620784608151591 Name LPM GPM GSM GSM/GPM [Mutations] (Lineage) TYHKWEFRALGDSGGRNKLSSSTDRIKNKVGLNSTEFFQNYPHNP 1-Initial 0 0 0 0.0% [] I-Q.......V...HT..IFPFANS.NK.PS.KNKAPSRYH.YKH 2-North-America-1 7860 15245 10279 67.4% [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,N460K,S477N,T478K,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I..ER.L......SHT...FPFANS.NKT.SRKNKAS.RYH.YKH 3-Europe-1 587 2461 566 23.0% [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-............DT...FPFANS.NKT..RKNKAV.RYH.YKH 4-United-Kingdom-1 182 857 454 53.0% [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..ER.L......SHT.T.FPFANS.NK..S.KNKA.SRYH.YKH 5-Asia-1 960 1106 635 57.4% [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..ER.L......SHT...FPFANS.NK..S.KNKAPSRYH.YKH 6-Oceania-1 174 720 415 57.6% [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-Q.......V...HT..IFPFANS..K.PS.KNKAPSRYH.YKH 7-South-America-1 54 311 155 49.8% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y144-,H146Q,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,R408S,N440K,V445P,G446S,N460K,S477N,T478K,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I-Q.......V...HT..IFPFAN..NK.PS.KNKAPSRYH.YKH 8-Africa-1 16 153 74 48.4% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y144-,H146Q,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,K417N,N440K,V445P,G446S,N460K,S477N,T478K,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I.............DT...FPFANS.NKT..RKNKAV.RYH.YKH 9-North-America-2 489 935 548 58.6% [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-K.......V...HT..IFPFANS.NK.PS.KNKAPSRYH.YKH 10-Europe-2 173 786 526 66.9% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y144-,H146K,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-.........G..DT...FPFANS.NKT..RKNKAV.RYH.YKH 11-United-Kingdom-2 136 178 52 29.2% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,Y144-,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,E1144Q] (Omicron_BA.4andBA.5) I.............DT...FPFANS.NK...R.NKAV.RYH.YKH 12-Asia-2 631 712 305 42.8% [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-...G----..L..S...FPFANS.NK..SR.NKAP.RYH.YKH 13-Oceania-2 58 58 48 82.8% [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-K.......V...HT..IFPFANS..K.PS.KNKAPSRYH.YKH 14-South-America-2 11 29 14 48.3% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y144-,H146K,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,R408S,N440K,V445P,G446S,N460K,S477N,T478K,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I-Q.......V...HT..IFP.AN..NK.PS.KNKAPSRYH.YKH 15-Africa-2 13 13 2 15.4% [T19I,L24-,P25-,P26-,A27S,D40X,K41X,V42X,F43X,R44X,S45X,S46X,V47X,L48X,H49X,S50X,T51X,Q52X,D53X,L54X,F55X,L56X,P57X,F58X,F59X,S60X,N61X,V62X,T63X,W64X,F65X,H66X,A67X,I68X,H69X,V70X,S71X,G72X,T73X,N74X,G75X,T76X,K77X,R78X,F79X,D80X,N81X,P82X,V83X,L84X,P85X,F86X,N87X,D88X,G89X,V90X,G142D,Y144-,H146Q,Y170X,V171X,S172X,Q173X,P174X,F175X,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,T376A,D405N,K417N,N440K,V445P,G446S,N460K,S477N,T478K,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I.............D....FPFANS.NKT..RKNKAV.RYH.YKH 16-North-America-3 101 174 78 44.8% [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-Q.......V...HT..IFPFAN..NK.PS.K.KAPSRYH.YKH 17-Europe-3 151 151 87 57.6% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y144-,H146Q,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,K417N,N440K,V445P,G446S,N460K,T478K,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I..N..........DT...FPFANS.NKT..RKNKAV.RYH.YKH 18-United-Kingdom-3 33 47 20 42.6% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,K147N,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....FPFANS.NK...R.NKAV.RYH.YKH 19-Asia-3 590 600 319 53.2% [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..ER.L......SHT...FPFANS.NK..SRKNKAI.RYH.YKH 20-Oceania-3 45 73 45 61.6% [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-Q.......V...H...IFPFANS.NK.PS.KNKAPSRYH.YKH 21-South-America-3 2 4 2 50.0% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y144-,H146Q,Q183E,V213E,G252V,G339H,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..IFP..N..NK.PS.KNKAPSRYH.YKH 22-Africa-3 7 7 2 28.6% [T19I,L24-,P25-,P26-,A27S,D40X,K41X,V42X,F43X,R44X,S45X,S46X,V47X,L48X,H49X,S50X,T51X,Q52X,D53X,L54X,F55X,L56X,P57X,F58X,F59X,S60X,N61X,V62X,T63X,W64X,F65X,H66X,A67X,I68X,H69X,V70X,S71X,G72X,T73X,N74X,G75X,T76X,K77X,R78X,F79X,D80X,N81X,P82X,V83X,L84X,P85X,F86X,N87X,D88X,G89X,V90X,G142D,Y144-,H146Q,Y170X,V171X,S172X,Q173X,P174X,F175X,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,D405N,K417N,N440K,V445P,G446S,N460K,S477N,T478K,E484A,F486P,F490S,Q498R,N501Y,Y505H,A570V,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I-............D....FPFANS.NKT..RKNKAV.RYH.YKH 23-North-America-4 89 220 89 40.5% [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-Q.......V...HT..IFPFANSVNK.PS.KNKAPSRYHSYKH 24-Europe-4 115 118 85 72.0% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y144-,H146Q,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,R408S,I410V,K417N,N440K,V445P,G446S,N460K,S477N,T478K,E484A,F486P,F490S,Q498R,N501Y,Y505H,P521S,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I-Q........G..HT..IFPFANS.NK.PS.KNKAPSRYHSYKH 25-United-Kingdom-4 31 134 59 44.0% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y144-,H146Q,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............DDT...FPFANS.NK...R.NKAV.RYH.YKH 26-Asia-4 121 121 93 76.9% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,G257D,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-...G----..L......FPFANS.NK..SM.NKAP.RYH.YKH 27-Oceania-4 19 28 24 85.7% [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-Q.......V...HTK.IFPFANS..K.PS.KNKAPSRYH.YKH 28-South-America-4 2 2 2 100.0% [T19I,L24-,P25-,P26-,A27S,V83A,G142X,Y144-,H146Q,Q183E,V213E,G252V,G339H,R346T,N354K,L368I,S371F,S373P,S375F,T376A,D405N,R408S,N440K,V445P,G446S,N460K,S477N,T478K,E484A,F486P,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I-K...........HT..IFPFANS.NK.PS.KNKAASRYH.YKH 29-Africa-4 1 1 1 100.0% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y144-,H146K,M177T,K182E,Q183E,V213E,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,V445P,G446S,N460K,S477N,T478K,E484A,F486A,F490S,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 31278 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 0.0000
Oceania T-1 0.0000
South-America T-1 0.0000
Africa T-1 0.0000
Global T-8 0.6667
North-America T-8 0.7266
Europe-minus-United-Kingdom T-8 0.6501
United-Kingdom T-8 0.7885
Asia T-8 0.4276
Oceania T-8 0.6243
South-America T-8 0.7172
Africa T-8 0.6081
Global T-15 0.7534
North-America T-15 0.8078
Europe-minus-United-Kingdom T-15 0.7042
United-Kingdom T-15 0.8509
Asia T-15 0.5997
Oceania T-15 0.7321
South-America T-15 0.8414
Africa T-15 0.7838
Global T-22 0.7871
North-America T-22 0.8180
Europe-minus-United-Kingdom T-22 0.7293
United-Kingdom T-22 0.8606
Asia T-22 0.7253
Oceania T-22 0.7834
South-America T-22 0.8552
Africa T-22 0.8784
Global T-29 0.8071
North-America T-29 0.8277
Europe-minus-United-Kingdom T-29 0.7529
United-Kingdom T-29 0.8684
Asia T-29 0.7753
Oceania T-29 0.8100
South-America T-29 0.8759
Africa T-29 0.8919
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 2023-02-28 to 2023-03-27. The number of sequences, broken out by continent is: Total: 31278, North-America: 11605, Europe-minus-United-Kingdom: 8053, United-Kingdom: 5480, Asia: 4984, Oceania: 937, South-America: 145, Africa: 74. 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.
