Summary

This strain contains 18 protein-level mutations:

  • 5 mutations in Spike protein: L452R, T478K, D614G, P681R, D950N
  • 3 mutations in N protein: D63G, R203M, G215C
  • 1 mutation in M protein: I82T
  • 1 mutation in NS3 protein: S26L
  • 2 mutations in NS7a protein: V82A, T120I
  • 1 mutation in NS9b protein: T60A
  • 1 mutation in NS9c protein: G50W
  • 2 mutations in NSP3 protein: A488S, P1469S
  • 1 mutation in NSP12 protein: P323L
  • 1 mutation in NSP14 protein: 413-415 GCD->LNY

We identified all possible linear viral peptides affected by these mutations. Whenever it was possible, we matched the reference peptide with the mutated one. For example, D -> L mutation transformed SDNGPQNQR to SLNGPQNQR. Cases when it was not meaningful included deletions and insertions at the flanks of the peptide, e.g., HV deletion in NVTWFHAIHV peptide.

Then, we predicted binding affinities between the selected peptides and frequent HLA alleles. Predictions were made with NetMHCpan-4.1 and NetMHCIIpan-4.0. The binding affinities were classifies into three groups:

  1. Tight binding (IC50 affinity ≤ 50 nM)
  2. Moderate binding (50 nM < IC50 affinity ≤ 500 nM)
  3. Weak/no binding (IC50 affinity > 500 nM)

Here we report HLA-peptide interactions whose affinity was altered by at least two folds. Note that mutations with empty set of altered interactions are not showed.

The total number of interactions between HLA-DRB1*11:01 and peptides affected by the mutations

Weaker binding was found for 21 epitopes, while stronger binding was found for 77 entries. There are 937 tight binders for the HLA-DRB1*11:01 in the reference immunopeptidome (IC50 affinity ≤ 50 nM); 2 of them became non-tight binders (0.2%) and 16 novel tight binders appeared (1.7%). To avoid possible divisions by zero, we used + 1 regularization term in denominators when calculating percentages.

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HLA-DRB1*11:01

Spike protein

L452R

Reference  DDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGS
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Mutated    DDFTGCVIAWNSNNLDSKVGGNYNYRYRLFRKSNLKPFERDISTEIYQAGS

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DRB1*11:01 GGNYNYLYRLFRKSN GGNYNYRYRLFRKSN 37 169
HLA-DRB1*11:01 KVGGNYNYLYRLFRKSN KVGGNYNYRYRLFRKSN 72 326
HLA-DRB1*11:01 VGGNYNYLYRLFRKSN VGGNYNYRYRLFRKSN 82 368
HLA-DRB1*11:01 KVGGNYNYLYRLFRK KVGGNYNYRYRLFRK 64 271
HLA-DRB1*11:01 SKVGGNYNYLYRLFRK SKVGGNYNYRYRLFRK 145 597
HLA-DRB1*11:01 DSKVGGNYNYLYRLFRK DSKVGGNYNYRYRLFRK 133 541
HLA-DRB1*11:01 SKVGGNYNYLYRLFR SKVGGNYNYRYRLFR 144 581
HLA-DRB1*11:01 DSKVGGNYNYLYRLFR DSKVGGNYNYRYRLFR 357 1364
HLA-DRB1*11:01 SKVGGNYNYLYRLFRKSN SKVGGNYNYRYRLFRKSN 281 1070
HLA-DRB1*11:01 LDSKVGGNYNYLYRLFR LDSKVGGNYNYRYRLFR 344 1295
HLA-DRB1*11:01 KVGGNYNYLYRLFRKS KVGGNYNYRYRLFRKS 114 416
HLA-DRB1*11:01 DSKVGGNYNYLYRLFRKSN DSKVGGNYNYRYRLFRKSN 134 485
HLA-DRB1*11:01 VGGNYNYLYRLFRKS VGGNYNYRYRLFRKS 50 179
HLA-DRB1*11:01 SKVGGNYNYLYRLFRKS SKVGGNYNYRYRLFRKS 102 357
HLA-DRB1*11:01 DSKVGGNYNYLYRLFRKS DSKVGGNYNYRYRLFRKS 383 1300
HLA-DRB1*11:01 LDSKVGGNYNYLYRLFRKSN LDSKVGGNYNYRYRLFRKSN 83 278
HLA-DRB1*11:01 NLDSKVGGNYNYLYRLFRK NLDSKVGGNYNYRYRLFRK 258 850
HLA-DRB1*11:01 LDSKVGGNYNYLYRLFRKS LDSKVGGNYNYRYRLFRKS 185 559
HLA-DRB1*11:01 NNLDSKVGGNYNYLYRLFRK NNLDSKVGGNYNYRYRLFRK 176 498
HLA-DRB1*11:01 NLDSKVGGNYNYLYRLFRKS NLDSKVGGNYNYRYRLFRKS 118 331

P681R

Reference  VNNSYECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLGAENSVA
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Mutated    VNNSYECDIPIGAGICASYQTQTNSRRRARSVASQSIIAYTMSLGAENSVA

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DRB1*11:01 YQTQTNSPRRARSVA YQTQTNSRRRARSVA 1740 414
HLA-DRB1*11:01 SYQTQTNSPRRARSV SYQTQTNSRRRARSV 1303 360
HLA-DRB1*11:01 SYQTQTNSPRRARSVASQSI SYQTQTNSRRRARSVASQSI 1338 399
HLA-DRB1*11:01 CASYQTQTNSPRRARSVASQ CASYQTQTNSRRRARSVASQ 1371 421
HLA-DRB1*11:01 ASYQTQTNSPRRARSVASQS ASYQTQTNSRRRARSVASQS 1320 407
HLA-DRB1*11:01 ICASYQTQTNSPRRARSVAS ICASYQTQTNSRRRARSVAS 1365 443
HLA-DRB1*11:01 ASYQTQTNSPRRARS ASYQTQTNSRRRARS 1184 394
HLA-DRB1*11:01 YQTQTNSPRRARSVASQSII YQTQTNSRRRARSVASQSII 1315 438
HLA-DRB1*11:01 GICASYQTQTNSPRRARSVA GICASYQTQTNSRRRARSVA 1397 484
HLA-DRB1*11:01 CASYQTQTNSPRRAR CASYQTQTNSRRRAR 1341 484
HLA-DRB1*11:01 QTQTNSPRRARSVASQSIIA QTQTNSRRRARSVASQSIIA 1351 495

NS9b protein

T60A

Reference  NNVGPKVYPIILRLGSPLSLNMARKTLNSLEDKAFQLTPIAVQMTKLATTE
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Mutated    NNVGPKVYPIILRLGSPLSLNMARKALNSLEDKAFQLTPIAVQMTKLATTE

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DRB1*11:01 SLNMARKTLNSLEDKAFQL SLNMARKALNSLEDKAFQL 977 321
HLA-DRB1*11:01 RLGSPLSLNMARKTLNSL RLGSPLSLNMARKALNSL 492 165
HLA-DRB1*11:01 SLNMARKTLNSLEDKA SLNMARKALNSLEDKA 520 175
HLA-DRB1*11:01 GSPLSLNMARKTLNSLED GSPLSLNMARKALNSLED 507 172
HLA-DRB1*11:01 LGSPLSLNMARKTLNSLE LGSPLSLNMARKALNSLE 501 170
HLA-DRB1*11:01 SLNMARKTLNSLEDKAF SLNMARKALNSLEDKAF 407 141
HLA-DRB1*11:01 LSLNMARKTLNSLEDKAFQ LSLNMARKALNSLEDKAFQ 348 121
HLA-DRB1*11:01 LRLGSPLSLNMARKTLNS LRLGSPLSLNMARKALNS 825 287
HLA-DRB1*11:01 PLSLNMARKTLNSLEDKAF PLSLNMARKALNSLEDKAF 212 74
HLA-DRB1*11:01 SPLSLNMARKTLNSLEDK SPLSLNMARKALNSLEDK 552 193
HLA-DRB1*11:01 PLSLNMARKTLNSLEDKA PLSLNMARKALNSLEDKA 667 234
HLA-DRB1*11:01 SLNMARKTLNSLEDKAFQLT SLNMARKALNSLEDKAFQLT 621 218
HLA-DRB1*11:01 LSLNMARKTLNSLEDKAF LSLNMARKALNSLEDKAF 933 334
HLA-DRB1*11:01 SPLSLNMARKTLNSLEDKA SPLSLNMARKALNSLEDKA 175 63
HLA-DRB1*11:01 LGSPLSLNMARKTLNSLED LGSPLSLNMARKALNSLED 152 55
HLA-DRB1*11:01 GSPLSLNMARKTLNSLEDK GSPLSLNMARKALNSLEDK 157 57
HLA-DRB1*11:01 RLGSPLSLNMARKTLNSLE RLGSPLSLNMARKALNSLE 153 56
HLA-DRB1*11:01 LRLGSPLSLNMARKTLNSL LRLGSPLSLNMARKALNSL 163 60
HLA-DRB1*11:01 LSLNMARKTLNSLEDKAFQL LSLNMARKALNSLEDKAFQL 231 86
HLA-DRB1*11:01 LSLNMARKTLNSLEDKA LSLNMARKALNSLEDKA 142 54
HLA-DRB1*11:01 SLNMARKTLNSLEDK SLNMARKALNSLEDK 168 64
HLA-DRB1*11:01 PLSLNMARKTLNSLEDK PLSLNMARKALNSLEDK 102 39
HLA-DRB1*11:01 LSLNMARKTLNSLEDK LSLNMARKALNSLEDK 168 65
HLA-DRB1*11:01 RLGSPLSLNMARKTLNS RLGSPLSLNMARKALNS 136 53
HLA-DRB1*11:01 PLSLNMARKTLNSLEDKAFQ PLSLNMARKALNSLEDKAFQ 127 50
HLA-DRB1*11:01 LGSPLSLNMARKTLNS LGSPLSLNMARKALNS 167 66
HLA-DRB1*11:01 ILRLGSPLSLNMARKTLNS ILRLGSPLSLNMARKALNS 258 102
HLA-DRB1*11:01 PLSLNMARKTLNSLED PLSLNMARKALNSLED 126 50
HLA-DRB1*11:01 GSPLSLNMARKTLNSLE GSPLSLNMARKALNSLE 83 33
HLA-DRB1*11:01 LGSPLSLNMARKTLNSL LGSPLSLNMARKALNSL 80 32
HLA-DRB1*11:01 SPLSLNMARKTLNSLED SPLSLNMARKALNSLED 87 35
HLA-DRB1*11:01 GSPLSLNMARKTLNSLEDKA GSPLSLNMARKALNSLEDKA 91 37
HLA-DRB1*11:01 SPLSLNMARKTLNSLE SPLSLNMARKALNSLE 110 45
HLA-DRB1*11:01 GSPLSLNMARKTLNSL GSPLSLNMARKALNSL 100 41
HLA-DRB1*11:01 LGSPLSLNMARKTLNSLEDK LGSPLSLNMARKALNSLEDK 85 35
HLA-DRB1*11:01 SPLSLNMARKTLNSLEDKAF SPLSLNMARKALNSLEDKAF 102 42
HLA-DRB1*11:01 RLGSPLSLNMARKTLN RLGSPLSLNMARKALN 344 143
HLA-DRB1*11:01 LGSPLSLNMARKTLN LGSPLSLNMARKALN 143 60
HLA-DRB1*11:01 LRLGSPLSLNMARKTLN LRLGSPLSLNMARKALN 269 113
HLA-DRB1*11:01 RLGSPLSLNMARKTLNSLED RLGSPLSLNMARKALNSLED 83 35
HLA-DRB1*11:01 LRLGSPLSLNMARKTLNSLE LRLGSPLSLNMARKALNSLE 85 36
HLA-DRB1*11:01 ILRLGSPLSLNMARKTLNSL ILRLGSPLSLNMARKALNSL 96 42
HLA-DRB1*11:01 LNMARKTLNSLEDKA LNMARKALNSLEDKA 944 413
HLA-DRB1*11:01 GSPLSLNMARKTLNS GSPLSLNMARKALNS 66 29
HLA-DRB1*11:01 LSLNMARKTLNSLED LSLNMARKALNSLED 63 28
HLA-DRB1*11:01 IILRLGSPLSLNMARKTLNS IILRLGSPLSLNMARKALNS 133 61
HLA-DRB1*11:01 SPLSLNMARKTLNSL SPLSLNMARKALNSL 42 20
HLA-DRB1*11:01 PLSLNMARKTLNSLE PLSLNMARKALNSLE 47 23

NSP3 protein

A488S

Reference  KDAPYIVGDVVQEGVLTAVVIPTKKAGGTTEMLAKALRKVPTDNYITTYPG
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Mutated    KDAPYIVGDVVQEGVLTAVVIPTKKSGGTTEMLAKALRKVPTDNYITTYPG

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DRB1*11:01 LTAVVIPTKKAGGTTEMLAK LTAVVIPTKKSGGTTEMLAK 474 983

NSP12 protein

P323L

Reference  CVNCLDDRCILHCANFNVLFSTVFPPTSFGPLVRKIFVDGVPFVVSTGYHF
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Mutated    CVNCLDDRCILHCANFNVLFSTVFPLTSFGPLVRKIFVDGVPFVVSTGYHF

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DRB1*11:01 STVFPPTSFGPLVRK STVFPLTSFGPLVRK 2376 314
HLA-DRB1*11:01 FSTVFPPTSFGPLVRKI FSTVFPLTSFGPLVRKI 2923 409
HLA-DRB1*11:01 TVFPPTSFGPLVRKI TVFPLTSFGPLVRKI 1773 257
HLA-DRB1*11:01 FSTVFPPTSFGPLVR FSTVFPLTSFGPLVR 2949 493
HLA-DRB1*11:01 LFSTVFPPTSFGPLVRK LFSTVFPLTSFGPLVRK 2782 492
HLA-DRB1*11:01 NVLFSTVFPPTSFGPLVRKI NVLFSTVFPLTSFGPLVRKI 1267 408
HLA-DRB1*11:01 TVFPPTSFGPLVRKIF TVFPLTSFGPLVRKIF 902 293
HLA-DRB1*11:01 STVFPPTSFGPLVRKIF STVFPLTSFGPLVRKIF 729 240
HLA-DRB1*11:01 LFSTVFPPTSFGPLVRKIF LFSTVFPLTSFGPLVRKIF 1150 447
HLA-DRB1*11:01 FNVLFSTVFPPTSFGPLVRK FNVLFSTVFPLTSFGPLVRK 1200 468
HLA-DRB1*11:01 VFPPTSFGPLVRKIF VFPLTSFGPLVRKIF 292 125
HLA-DRB1*11:01 VLFSTVFPPTSFGPLVRKIF VLFSTVFPLTSFGPLVRKIF 625 279
HLA-DRB1*11:01 VFPPTSFGPLVRKIFVD VFPLTSFGPLVRKIFVD 387 176
HLA-DRB1*11:01 NVLFSTVFPPTSFGP NVLFSTVFPLTSFGP 708 336
HLA-DRB1*11:01 TVFPPTSFGPLVRKIFV TVFPLTSFGPLVRKIFV 324 157
HLA-DRB1*11:01 FPPTSFGPLVRKIFVDG FPLTSFGPLVRKIFVDG 428 208
HLA-DRB1*11:01 VFPPTSFGPLVRKIFV VFPLTSFGPLVRKIFV 413 203
HLA-DRB1*11:01 FPPTSFGPLVRKIFVD FPLTSFGPLVRKIFVD 492 245