SHIVER

SARS CoV-2 Historically Identified Variants in Epitope Regions

SHIVER: SARS CoV-2 Historically Identified Variants in Epitope Regions

SHIVER identifies sets of variant forms of the SARS CoV-2 virus with a focus on just the NTD and RBD neutralizing antibody epitope regions of the Spike protein, chosen to maximize coverage globally and/or on separate continents[*], depending on which of several strategies is employed.

The first variant in the input alignment is taken as the reference sequence, and should be the ancestral Wuhan variant to ensure epitope regions are chosen appropriately. The epitope regions in Spike that are featured as are defined as: The NTD supersite includes Spike positions 13-20, 140-158, and 242-264 (note, however, that site 18 is not included in the analysis because it is so variable that both the ancestral L18 form and the common variant L18F are very often both found in significant numbers among Variants of Interest).

The NTD supersite sites selected are for inclusion are based on:

Sites 14-20, 140-158, and 245-264: N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2 McCallum, M. et al. bioRxiv doi: 10.1101/2021.01.14.426475

Site 13: SARS-CoV-2 immune evasion by variant B.1.427/B.1.429 McCallum, M. et al. bioRxiv, 2021/04/07 doi: 10.1101/2021.03.31.437925 PMC8020983

Sites 242-244: SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma Wibmer, C. et al. bioRxiv, doi: 10.1101/2021.01.18.427166

Sites 330-521: The RBD region includes positions 330-521, based on a synthesis of the literature from early 2020.

All distinct variants found within these boundaries are identified and tallied, and the most common variants are selected. Windows in time can be selected to reflect more recently emerging patterns in variation in key epitope regions.

[*] Note that the UK is treated as a separate continent because so much of the sequencing has been from the UK.

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.

This run uses sequences sampled from 2021-08-01 to 2021-08-31.
The number of sequences, broken out by continent is:
Total: 186242, Europe-w/o-United-Kingdom: 70320, United-Kingdom: 62597, North-America: 46194, Asia: 4320, South-America: 1736, Oceania: 1050, Africa: 25.
Note: the focus here is specifically on the epitope region: NTD-18+RBD
Sites: 13-17,19,20,140-158,242-264,330-521

Table of Variants

In the table below, the first column is the pattern at sites where differences occur, relative to initial (Wuhan) sequence, with site numbers read down vertically).

LPM = Local Pattern Matches = # of seqs in continent that match over RBD+NTD GPM = Global Pattern Matches = # of seqs in world that match over RBD+NTD
GSM = Global Sequence Matches = # of seqs that match over whole Spike protein

   1111111111122222222223344444444555
1124444444455544445555554601445789012
6900123345867867890123586757062840130 Name                    LPM    GPM    GSM  GSM/GPM [Mutations] (Lineage)
VTTFLGV-YYNEFRRSYLTPGDSWRVDKNGLTEFNLA 1-Initial              2977   2977     17     0.6% [] (Ancestral)
.R...D.....G--................RK..... 2-Europe-1            45333 135960  49613    36.5% [T19R,G142D,E156G,F157-,R158-,L452R,T478K,D614G,P681R,D950N] (B.1.617.2=Delta)
.R...D...H.G--................RK..... 3-United-Kingdom-1     1568   1596   1205    75.5% [T19R,T95I,G142D,Y145H,E156G,F157-,R158-,A222V,L452R,T478K,D614G,P681R,D950N] (Delta+A222V)
.R.........G--................RK..... 4-North-America-1     13417  27018  10821    40.1% [T19R,E156G,F157-,R158-,L452R,T478K,D614G,P681R,D950N] (B.1.617.2=Delta)
........-.........................Y.. 5-Asia-1                139   1760    865    49.1% [H69-,V70-,Y144-,N501Y,A570D,D614G,P681H,T716I,S982A,D1118H] (B.1.1.7=Alpha)
..N........................T....K.Y.. 6-South-America-1       452    753    342    45.4% [L18F,T20N,P26S,D138Y,R190S,K417T,E484K,N501Y,D614G,H655Y,T1027I,V1176F] (P.1=Gamma)
FR...D.....G--................RK..... 7-Oceania-1               7    262    124    47.3% [V16F,T19R,T95I,G142D,E156G,F157-,R158-,L452R,T478K,D614G,P681R,D950N,I1179V] (B.1.617.2=Delta)
........-......................K..... 8-Africa-1                1      2      1    50.0% [P9L,P25L,C136F,Y144-,T478K,D614G] 
.R...D.....G--....I...........RK..... 9-Europe-2              634    697    258    37.0% [T19R,T29A,G142D,E156G,F157-,R158-,T250I,L452R,T478K,D614G,P681R,D950N] (B.1.617.2=Delta)
.R...D.....G--.....L..........RK..... 10-United-Kingdom-2     297    845    495    58.6% [T19R,G142D,E156G,F157-,R158-,P251L,L452R,T478K,D614G,P681R,D950N] (B.1.617.2=Delta)
.......TSN..............K.......K.Y.. 11-North-America-2      187    217    113    52.1% [T95I,+143T,Y144S,Y145N,R346K,E484K,N501Y,D614G,P681H,D950N] (B.1.621)
.R............................RK..... 12-Asia-2               105    283    108    38.2% [T19R,L452R,T478K,D614G,P681R,D950N] 
..............N-------........Q..S... 13-South-America-2       25     46     19    41.3% [G75V,T76I,R246N,S247-,Y248-,L249-,T250-,P251-,G252-,D253-,L452Q,F490S,D614G,T859N] (C.37=Lambda)
.R...D.....G--.........L...N..RK..... 14-Oceania-2              2     64     48    75.0% [T19R,T95I,G142D,E156G,F157-,R158-,W258L,K417N,L452R,T478K,D614G,P681R,D950N] (Delta-AY.1)
........-..............L........K.... 15-Africa-2               1      1      1   100.0% [D80Y,T95I,Y144-,W258L,E484K,D614G,P681H,D796H] (B.1.1.318)
..................................Y.. 16-Europe-3             565    566    377    66.6% [N501Y,D614G] (G-clade)
.R...D.....G--...............VRK..... 17-United-Kingdom-3     166    255    160    62.7% [T19R,T95I,G142D,E156G,F157-,R158-,G446V,L452R,T478K,D614G,P681R,D950N] (B.1.617.2=Delta)
.R...D.....G--...........L....RK..... 18-North-America-3      106    118     84    71.2% [T19R,G142D,E156G,F157-,R158-,A222V,V367L,L452R,T478K,D614G,P681R,D950N] (Delta+A222V)
........-.......................K.Y.. 19-Asia-3                32     45     31    68.9% [H69-,V70-,Y144-,E484K,N501Y,A570D,D614G,P681H,T716I,S982A,D1118H] (Alpha+E484K)
..N.............................K.Y.. 20-South-America-3       12     15      3    20.0% [L18F,T20N,P26S,D138Y,R190S,E484K,N501Y,D614G,H655Y,P681H,R683W,T1027I,V1176F] (P.1=Gamma)
.R.........G--................RK....S 21-Oceania-3              1      8      3    37.5% [T19R,E156G,F157-,R158-,L452R,T478K,A520S,D614G,P681R,D950N] (B.1.617.2=Delta)
.R.........G--....S.......Y...RK..... 22-Africa-3               1      1      1   100.0% [T19R,E156G,F157-,R158-,A222V,T250S,D405Y,L452R,T478K,D614G,P681R,D950N] (Delta+A222V)
.R.........G--.....L..........RK..... 23-Europe-4             513    526    394    74.9% [T19R,E156G,F157-,R158-,P251L,L452R,T478K,D614G,P681R,D950N] (B.1.617.2=Delta)
.R...D....SG--................RK..... 24-United-Kingdom-4     152    154    148    96.1% [T19R,T95I,G142D,N148S,E156G,F157-,R158-,L452R,T478K,D614G,P681R,D950N] (B.1.617.2=Delta)
.R...D.....G--.............N..RK..... 25-North-America-4       78    107     72    67.3% [T19R,V70F,G142D,E156G,F157-,R158-,A222V,K417N,L452R,T478K,D614G,P681R,D950N] (Delta-AY.2)
............................K...K.... 26-Asia-4                17     36     20    55.6% [I210T,N440K,E484K,D614G,D936N,S939F,T1027I] (B.1.619)
..N----.-..................T....K.Y.. 27-South-America-4        9      9      5    55.6% [L18F,T20N,P26S,D138-,P139Y,F140-,L141-,G142-,V143-,Y144-,R190S,K417T,E484K,N501Y,D614G,H655Y,T1027I,V1176F] (P.1=Gamma)
.R...D.....G--........F.......RK..... 28-Oceania-4              1    295    145    49.2% [T19R,T95I,G142D,E156G,F157-,R158-,S255F,L452R,T478K,D614G,P681R,D950N] (B.1.617.2=Delta)
.R.........G--................RK...F. 29-Africa-4               1      2      1    50.0% [T19R,E156G,F157-,R158-,L452R,T478K,L513F,D614G,P681R,T719I,D950N] (B.1.617.2=Delta)

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 NTD-18+RBD) to one of the first n variants. (Here, 'T' corresponds to the Taketurns strategy.) The coverage table is based on 186242 sequences.

                Continent Name Coverage

                   Global T-1    0.0160
Europe-w/o-United-Kingdom T-1    0.0422
           United-Kingdom T-1    0.0000
            North-America T-1    0.0001
                     Asia T-1    0.0002
            South-America T-1    0.0017
                  Oceania T-1    0.0000
                   Africa T-1    0.0400

                   Global T-8    0.9146
Europe-w/o-United-Kingdom T-8    0.8716
           United-Kingdom T-8    0.9433
            North-America T-8    0.9396
                     Asia T-8    0.9144
            South-America T-8    0.9078
                  Oceania T-8    0.9933
                   Africa T-8    0.7600

                   Global T-15   0.9261
Europe-w/o-United-Kingdom T-15   0.8897
           United-Kingdom T-15   0.9488
            North-America T-15   0.9473
                     Asia T-15   0.9407
            South-America T-15   0.9424
                  Oceania T-15   0.9962
                   Africa T-15   0.8000

                   Global T-22   0.9315
Europe-w/o-United-Kingdom T-22   0.8987
           United-Kingdom T-22   0.9516
            North-America T-22   0.9504
                     Asia T-22   0.9486
            South-America T-22   0.9505
                  Oceania T-22   0.9981
                   Africa T-22   0.8400

                   Global T-29   0.9376
Europe-w/o-United-Kingdom T-29   0.9090
           United-Kingdom T-29   0.9560
            North-America T-29   0.9525
                     Asia T-29   0.9539
            South-America T-29   0.9562
                  Oceania T-29   0.9990
                   Africa T-29   0.8800