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
111111111112222222233333333444444444444444455666 1444445555554445555534567777001444455677889900578 9456790236783451236796681356587045602078460815591 Name LPM GPM GSM GSM/GPM [Mutations] (Lineage) TYYHKNKWMEFRALHPGDSGGRKLSSSTDRKNKVGNLNSTEFFQNYHNP 1-Initial 1 1 1 100.0% [] I...................D...FPFANSNK....R.NKAV.RYHYKH 2-North-America-1 4283 12729 7738 60.8% [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...................DT..FPFANSNK....R.NKAV.RYHYKH 3-Europe-1 4128 9329 6192 66.4% [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...................DT..FPFANSNKT...RKNKAV.RYHYKH 4-Asia-1 770 9684 8061 83.2% [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-..................D...FPFANSNKT...RKNKAV.RYHYKH 5-United-Kingdom-1 354 1973 1635 82.9% [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...E..R..L........SHT..FPFANSNK..S.RKNKAI.RYHYKH 6-Oceania-1 457 482 448 92.9% [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...................DT..FPFAN.NKT...RKNKAV.RYHYKH 7-South-America-1 43 120 95 79.2% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,G339D,R346T,S371F,S373P,S375F,T376A,D405N,K417N,N440K,K444T,L452R,N460K,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I.Q-............V...HT.IFPFANSNK.PS..KNKASSRYHYKH 8-Africa-1 6 1077 789 73.3% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y145Q,H146-,Q183E,V213E,G252V,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,V445P,G446S,N460K,S477N,T478K,E484A,F486S,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I...................D...FPFANSNKT...RKNKAV.RYHYKH 9-North-America-2 3573 5405 3669 67.9% [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-..................DT..FPFANSNKT...RKNKAV.RYHYKH 10-Europe-2 1294 2038 1771 86.9% [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...................D...FPFAN.NK....R.NKAV.RYHYKH 11-Asia-2 387 419 210 50.1% [T19I,L24-,P25-,P26-,A27S,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...E..R..L........SHTT.FPFANSNK..S..KNKA.SRYHYKH 12-United-Kingdom-2 288 1777 1424 80.1% [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...E..R..L........SHT..FPFANSNK..S..KNKAPSRYHYKH 13-Oceania-2 372 408 377 92.4% [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...................D...FPFAN.NKT...RKNKAV.RYHYKH 14-South-America-2 18 51 38 74.5% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,K417N,N440K,K444T,L452R,N460K,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I-..................DT..FPFANSNK....R.NKAV.RYHYKH 15-Africa-2 5 428 302 70.6% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,Y144-,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...................D...FPFANSNK...DR.NKAV.RYHYKH 16-North-America-3 253 799 517 64.7% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,N450D,L452R,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.4andBA.5) I...................DI..FPFANSNK....R.NKAV.RYHYKH 17-Europe-3 304 450 351 78.0% [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-..................D...FPFANSNK....R.NKAV.RYHYKH 18-Asia-3 99 475 381 80.2% [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...E..R..L........SHT..FPFANSNKT.S.RKNKAS.RYHYKH 19-United-Kingdom-3 145 388 269 69.3% [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...E..R..L........SHT..FPFANSNK..S..KNKAS.RYHYKH 20-Oceania-3 93 424 147 34.7% [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,F486S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I.Q-.............G..HT.IFPFAN.NK.PS..KNKASSRYHYKH 21-South-America-3 18 18 14 77.8% [T19I,L24-,P25-,P26-,A27S,V83A,G142D,Y145Q,H146-,Q183E,V213E,D253G,G339H,R346T,L368I,S371F,S373P,S375F,T376A,D405N,K417N,N440K,V445P,G446S,N460K,S477N,T478K,E484A,F486S,F490S,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I..............L....DT..FPFANSNKT...RKNKAV.RYHYKH 22-Africa-3 4 67 42 62.7% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,P251L,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...................DS..FPFANSNK....R.NKAV.RYHYKH 23-North-America-4 223 469 343 73.1% [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,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.4andBA.5) I...--..............D...FPFANSNK....R.NKAV.RYHYKH 24-Europe-4 223 225 207 92.0% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,K147-,N149-,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,P1162S] (Omicron_BA.4andBA.5) I.......T.....N....DD...FPFANSNKR..DMKNKR..RYHYKH 25-Asia-4 58 391 301 77.0% [T19I,L24-,P25-,P26-,A27S,G142D,M153T,N164K,V213G,H245N,G257D,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,K444R,N450D,L452M,N460K,S477N,T478K,E484R,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I................G..DT..FPFANSNKT...RKNKAV.RYHYKH 26-United-Kingdom-4 51 98 90 91.8% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,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] (Omicron_BA.4andBA.5) I-.......G----....L.....FPFANSNK..S.M.NKAP.RYHYKH 27-Oceania-4 56 64 59 92.2% [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...................D...FPFAN.NKN...RKNKAV.RYHYKH 28-South-America-4 13 13 7 53.8% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,V213G,G339D,S371F,S373P,S375F,T376A,D405N,K417N,N440K,K444N,L452R,N460K,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] I.....E.............D...FPFANSNKN...RKNKAV.RYHYKH 29-Africa-4 3 172 112 65.1% [T19I,L24-,P25-,P26-,A27S,H69-,V70-,G142D,K150E,V213G,G339D,S371F,S373P,S375F,T376A,D405N,R408S,K417N,N440K,K444N,L452R,N460K,S477N,T478K,E484A,F486V,Q498R,N501Y,Y505H,D614G,H655Y,N679K,P681H,N764K,D796Y,Q954H,N969K] (Omicron_BA.4andBA.5)
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 61475 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 0.0002
Oceania T-1 0.0000
South-America T-1 0.0000
Africa T-1 0.0000
Global T-8 0.5758
North-America T-8 0.5631
Europe-minus-United-Kingdom T-8 0.5856
Asia T-8 0.6666
United-Kingdom T-8 0.5155
Oceania T-8 0.4774
South-America T-8 0.3597
Africa T-8 0.7368
Global T-15 0.7470
North-America T-15 0.7642
Europe-minus-United-Kingdom T-15 0.7239
Asia T-15 0.7913
United-Kingdom T-15 0.7281
Oceania T-15 0.7216
South-America T-15 0.4768
Africa T-15 0.8158
Global T-22 0.7896
North-America T-22 0.7969
Europe-minus-United-Kingdom T-22 0.7727
Asia T-22 0.8226
United-Kingdom T-22 0.7922
Oceania T-22 0.7847
South-America T-22 0.5313
Africa T-22 0.8509
Global T-29 0.8129
North-America T-29 0.8127
Europe-minus-United-Kingdom T-29 0.8048
Asia T-29 0.8340
United-Kingdom T-29 0.8167
Oceania T-29 0.8240
South-America T-29 0.5695
Africa T-29 0.9035
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 2022-11-06 to 2022-12-04. The number of sequences, broken out by continent is: Total: 61475, North-America: 21773, Europe-minus-United-Kingdom: 21296, Asia: 9109, United-Kingdom: 4413, Oceania: 4403, South-America: 367, Africa: 114. 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.
