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SHIVER

SARS CoV-2 Historically Identified Variants in Epitope Regions

Last update: Mar 9, 2024

Dates of current data

Variants   Strategy   Reference

Variants: Delta and Omicron Variants
Strategy: Take turns
Reference strain: Wuhan reference
Early 2021 Variants color key
Delta Variants color key
Delta Omicron Variants color key

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

    111112222223333333444444444444445566
1112444554455664566777001444557777880177
4790146562907013358123054279232589061757 Name                    LPM    GPM    GSM  GSM/GPM [Mutations] (Lineage)
QMLFDHNSGNGDAADRTLF-FAKSNHDWLFAKK-KFHPKR 1-Initial                49     49     27    55.1% [] 
............................S........... 2-North-America-1      4183   5165   2988    57.9% [L452S] 
.---........................S........... 3-Asia-1                130    436    220    50.5% [M17-,P18-,L19-,F20-,L452S] 
........................K...S........... 4-Europe-1               13     15      5    33.3% [N414K,L452S] 
.---.Q.FRHV...ATKI....R..P.LFL..NVAS...H 5-Oceania-1              11     33     15    45.5% [M17-,P18-,L19-,F20-,T25R,L51S,Q53H,+69HV,V82A,F126V,H144Q,S155F,G156R,Q181E,+208N,I209L,G210E,F213L,N242H,G249V,D261A,V329I,R343T,T353K,L365I,K400R,H442P,W449L,L452F,F453L,K478N,+479V,K480A,F486S,K550E,V566A,S617P,R677H,S700L,F935S,L1139P] 
.---.QTFRH.G..ATKI.FS-R..PNL...TNVAS.S.H 6-United-Kingdom-1       15     24     10    41.7% [M17-,P18-,L19-,F20-,T25R,L51S,+69HV,K76R,V82A,F126V,H144Q,N146T,S155F,G156R,Q181E,N183I,F184-,+208N,I209L,G210E,F213L,N242H,D250G,D261A,V329I,R343T,T353K,L365I,+371F,F372S,A373-,K400R,H442P,D447N,W449L,K475T,K478N,+479V,K480A,F486S,P517S,K550E,V566A,S617P,R677H,F935S,L1139P] 
.---...................R....S........... 7-South-America-1         6      8      7    87.5% [M17-,P18-,L19-,F20-,S405R,L452S] 
..................S...R.....S........... 8-Africa-1                4      4      2    50.0% [F368S,K400R,L452S,I580V,S700L] 
...............T............S........... 9-North-America-2       193    209     69    33.0% [F60S,R343T,L452S,A1083S] 
............................S....VE..... 10-Asia-2                78     78     31    39.7% [+27XXX,L51X,L452S,+479V,K480E] 
.......................R....S........... 11-Europe-2               9    140     88    62.9% [S405R,L452S] 
............................SL.......... 12-Oceania-2              7    103     50    48.5% [L452S,F453L] 
.---...........T............S........... 13-United-Kingdom-2       3     12      4    33.3% [M17-,P18-,L19-,F20-,R343T,L452S] 
......................R.....S........... 14-South-America-2        3     16      6    37.5% [K400R,L452S] 
.---G..........T........K...S........... 15-Africa-2               3      3      1    33.3% [M17-,P18-,L19-,F20-,N21X,L22X,I23X,T24X,T25X,T26X,Q27X,+27XXX,D141G,R343T,N414K,L452S] 
...............T............SL.......... 16-North-America-3       44     50      7    14.0% [R343T,L452S,F453L] 
K---.Q.FRHV...ATKI....R..PNLFL..NVAS...H 17-Asia-3                12     15      9    60.0% [Q14K,M17-,P18-,L19-,F20-,T25R,L51S,Q53H,+69HV,V82A,F126V,H144Q,S155F,G156R,Q181E,+208N,I209L,G210E,F213L,N242H,G249V,D261A,V329I,R343T,T353K,L365I,K400R,H442P,D447N,W449L,L452F,F453L,K478N,+479V,K480A,F486S,K550E,V566A,S617P,R677H,F935S,L1139P] 
.---........................SL.......... 18-Europe-3               4     10      3    30.0% [M17-,P18-,L19-,F20-,L452S,F453L,A684V] 
............................S.........R. 19-Oceania-3              2      6      6   100.0% [L452S,K675R] 
............................S.......Y... 20-United-Kingdom-3       3     16      8    50.0% [L452S,H501Y] 
.---.Q.FRHV...ATKI....R..PNLFLV.NVAS...H 21-South-America-3        2     14      4    28.6% [M17-,P18-,L19-,F20-,T25R,L51S,+69HV,V82A,F126V,H144Q,S155F,G156R,Q181E,+208N,I209L,G210E,F213L,N242H,G249V,D261A,V329I,R343T,T353K,L365I,K400R,H442P,D447N,W449L,L452F,F453L,A472V,K478N,+479V,K480A,F486S,K550E,V566A,S617P,R677H,F935S,L1139P] 
...............T......R.....S........... 22-Africa-3               3      3      3   100.0% [R343T,K400R,L452S] 
.....Q......................S........... 23-North-America-4       29     30     24    80.0% [H144Q,L452S,T568I] 
............................SL...VE..... 24-Asia-4                11     11      2    18.2% [+27XXX,L452S,F453L,+479V,K480E] 
.---.Q.FRHV...ATKI....R..PNLFL..NVAS...H 25-Europe-4               4     21      9    42.9% [M17-,P18-,L19-,F20-,T25R,L51S,Q53H,+69HV,V82A,F126V,H144Q,S155F,G156R,Q181E,+208N,I209L,G210E,F213L,N242H,G249V,D261A,V329I,R343T,T353K,L365I,K400R,H442P,D447N,W449L,L452F,F453L,K478N,+479V,K480A,F486S,K550E,V566A,S617P,R677H,F935S,L1139P] 
............TV..............S........... 26-Oceania-4              2      2      2   100.0% [S32F,A257T,A260V,L452S] 
.---.Q.FRHV...ATKI....R..PNL.L.RNVAS...H 27-United-Kingdom-4       2      7      4    57.1% [M17-,P18-,L19-,F20-,T25R,L51S,+69HV,V82A,F126V,H144Q,S155F,G156R,E178V,K180Q,Q181E,+208N,I209L,G210E,F213L,N242H,G249V,D261A,V329I,R343T,T353K,L365I,K400R,H442P,D447N,W449L,F453L,K475R,K478N,+479V,K480A,F486S,V566A,S617P,R677H,A697V,F935S,L1139P] 
.---.K.FRHV...ATKI....R..PNLFLV.NVAS...H 28-South-America-4        1      3      1    33.3% [M17-,P18-,L19-,F20-,T25R,L51S,+69HV,V82A,F126V,H144K,S155F,G156R,Q181E,+208N,I209L,G210E,F213L,N242H,G249V,D261A,V329I,R343T,T353K,L365I,K400R,H442P,D447N,W449L,L452F,F453L,A472V,K478N,+479V,K480A,F486S,K550G,V566A,S617P,Q673R,R677H,F935S,L1139P] 
.---...........T......R.....S........... 29-Africa-4               1      1      1   100.0% [M17-,P18-,L19-,F20-,N21X,L22X,I23X,T24X,T25X,T26X,Q27X,+27XXX,S28X,L174F,R343T,K400R,L452S,L1230X,C1231X,C1232X] 

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 7173 sequences.

                Continent Name Coverage

                     Global T-1    0.0068
              North-America T-1    0.0037
                       Asia T-1    0.0018
Europe-minus-United-Kingdom T-1    0.0155
                    Oceania T-1    0.0305
             United-Kingdom T-1    0.0368
              South-America T-1    0.0000
                     Africa T-1    0.0000

                     Global T-8    0.7994
              North-America T-8    0.8193
                       Asia T-8    0.6011
Europe-minus-United-Kingdom T-8    0.7888
                    Oceania T-8    0.8659
             United-Kingdom T-8    0.7831
              South-America T-8    0.8056
                     Africa T-8    0.2667

                     Global T-15   0.8776
              North-America T-15   0.8938
                       Asia T-15   0.7766
Europe-minus-United-Kingdom T-15   0.8391
                    Oceania T-15   0.8994
             United-Kingdom T-15   0.8309
              South-America T-15   0.8750
                     Africa T-15   0.5333

                     Global T-22   0.8935
              North-America T-22   0.9070
                       Asia T-22   0.8050
Europe-minus-United-Kingdom T-22   0.8547
                    Oceania T-22   0.9238
             United-Kingdom T-22   0.8529
              South-America T-22   0.9028
                     Africa T-22   0.7333

                     Global T-29   0.9039
              North-America T-29   0.9155
                       Asia T-29   0.8369
Europe-minus-United-Kingdom T-29   0.8624
                    Oceania T-29   0.9299
             United-Kingdom T-29   0.8640
              South-America T-29   0.9167
                     Africa T-29   0.8000

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 2024-02-08 to 2024-03-06. The number of sequences, broken out by continent is: Total: 7173, North-America: 5406, Asia: 564, Europe-minus-United-Kingdom: 516, Oceania: 328, United-Kingdom: 272, South-America: 72, Africa: 15. 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.


 

last modified: Wed May 24 14:06 2023

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