Summary

This strain contains 11 protein-level mutations:

  • 3 mutations in Spike protein: E484K, D614G, V1176F
  • 4 mutations in N protein: A119S, 203-204 RG->KR, M234I, G238C
  • 1 mutation in NS9c protein: G50N
  • 1 mutation in NSP5 protein: L205V
  • 1 mutation in NSP7 protein: L71F
  • 1 mutation in NSP12 protein: P323L

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-A*02:02 and peptides affected by the mutations

Weaker binding was found for 15 epitopes, while stronger binding was found for 24 entries. There are 672 tight binders for the HLA-A*02:02 in the reference immunopeptidome (IC50 affinity ≤ 50 nM); 2 of them became non-tight binders (0.3%) and 7 novel tight binders appeared (1.0%). To avoid possible divisions by zero, we used + 1 regularization term in denominators when calculating percentages.

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HLA-A*02:02

Spike protein

D614G

Reference  PCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTG
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Mutated    PCSFGGVSVITPGTNTSNQVAVLYQGVNCTEVPVAIHADQLTPTWRVYSTG

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 DVNCTEVPV GVNCTEVPV 4099 213
HLA-A*02:02 QVAVLYQDV QVAVLYQGV 1107 188
HLA-A*02:02 NQVAVLYQDV NQVAVLYQGV 269 116

V1176F

Reference  ELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQ
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Mutated    ELDKYFKNHTSPDVDLGDISGINASFVNIQKEIDRLNEVAKNLNESLIDLQ

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 GDISGINASV GDISGINASF 71 3625
HLA-A*02:02 LGDISGINASV LGDISGINASF 208 8728
HLA-A*02:02 VDLGDISGINASV VDLGDISGINASF 413 11912
HLA-A*02:02 VVNIQKEIDRLNEV FVNIQKEIDRLNEV 2908 166

N protein

A119S

Reference  IRGGDGKMKDLSPRWYFYYLGTGPEAGLPYGANKDGIIWVATEGALNTPKD
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Mutated    IRGGDGKMKDLSPRWYFYYLGTGPESGLPYGANKDGIIWVATEGALNTPKD

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 YLGTGPEAGLPYGA YLGTGPESGLPYGA 155 318

NS9c protein

G50N

Reference  AAVKPLLVPHHVVATVQEIQLQAAVGELLLLEWLAMAVMLLLLCCCLTD
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Mutated    AAVKPLLVPHHVVATVQEIQLQAAVNELLLLEWLAMAVMLLLLCCCLTD

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 QLQAAVGEL QLQAAVNEL 92 28
HLA-A*02:02 IQLQAAVGEL IQLQAAVNEL 170 58
HLA-A*02:02 LQAAVGELL LQAAVNELL 44 17
HLA-A*02:02 QLQAAVGELL QLQAAVNELL 35 15
HLA-A*02:02 IQLQAAVGELL IQLQAAVNELL 724 313

NSP5 protein

L205V

Reference  NFYGPFVDRQTAQAAGTDTTITVNVLAWLYAAVINGDRWFLNRFTTTLNDF
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Mutated    NFYGPFVDRQTAQAAGTDTTITVNVVAWLYAAVINGDRWFLNRFTTTLNDF

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 VLAWLYAA VVAWLYAA 349 4233
HLA-A*02:02 VLAWLYAAVI VVAWLYAAVI 34 298
HLA-A*02:02 VNVLAWLYAAV VNVVAWLYAAV 192 1421
HLA-A*02:02 TVNVLAWLYAAV TVNVVAWLYAAV 114 744
HLA-A*02:02 ITVNVLAWLYAAV ITVNVVAWLYAAV 152 761
HLA-A*02:02 TITVNVLAWLYAAV TITVNVVAWLYAAV 403 1845
HLA-A*02:02 VLAWLYAAV VVAWLYAAV 3 13
HLA-A*02:02 NVLAWLYAAV NVVAWLYAAV 19 64

NSP7 protein

L71F

Reference  TEAFEKMVSLLSVLLSMQGAVDINKLCEEMLDNRATLQ
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Mutated    TEAFEKMVSLLSVLLSMQGAVDINKFCEEMLDNRATLQ

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 SMQGAVDINKL SMQGAVDINKF 382 10562
HLA-A*02:02 MQGAVDINKL MQGAVDINKF 359 7270
HLA-A*02:02 LCEEMLDNRATL FCEEMLDNRATL 1191 137
HLA-A*02:02 KLCEEMLDNRATL KFCEEMLDNRATL 278 1870

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-A*02:02 FPPTSFGPLV FPLTSFGPLV 7237 18
HLA-A*02:02 NVLFSTVFPP NVLFSTVFPL 1088 17
HLA-A*02:02 FNVLFSTVFPP FNVLFSTVFPL 1014 16
HLA-A*02:02 ANFNVLFSTVFPP ANFNVLFSTVFPL 3126 53
HLA-A*02:02 LFSTVFPP LFSTVFPL 9311 167
HLA-A*02:02 NFNVLFSTVFPP NFNVLFSTVFPL 2542 47
HLA-A*02:02 VLFSTVFPP VLFSTVFPL 269 5
HLA-A*02:02 FNVLFSTVFPPT FNVLFSTVFPLT 4116 110
HLA-A*02:02 FNVLFSTVFPPTS FNVLFSTVFPLTS 10920 497
HLA-A*02:02 FSTVFPPTSFGPLV FSTVFPLTSFGPLV 6958 322
HLA-A*02:02 CANFNVLFSTVFPP CANFNVLFSTVFPL 8183 391
HLA-A*02:02 VLFSTVFPPTS VLFSTVFPLTS 1210 377
HLA-A*02:02 VLFSTVFPPT VLFSTVFPLT 113 44
HLA-A*02:02 TVFPPTSFGPLV TVFPLTSFGPLV 789 343