Summary

This strain contains 12 protein-level mutations:

  • 1 mutation in Spike protein: D614G
  • 3 mutations in N protein: 203-204 RG->KR, M234I, P279S
  • 1 mutation in NS8 protein: G8R
  • 1 mutation in NS9c protein: G50N
  • 1 mutation in NSP2 protein: K81N
  • 1 mutation in NSP12 protein: P323L
  • 2 mutations in NSP14 protein: P43L, D345Y
  • 1 mutation in NSP15 protein: H337Y
  • 1 mutation in NSP16 protein: R287I

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*04:04 and peptides affected by the mutations

Weaker binding was not found, while stronger binding was found for 70 entries. There are 473 tight binders for the HLA-DRB1*04:04 in the reference immunopeptidome (IC50 affinity ≤ 50 nM); 0 of them became non-tight binders (0.0%) and 11 novel tight binders appeared (2.3%). To avoid possible divisions by zero, we used + 1 regularization term in denominators when calculating percentages.

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HLA-DRB1*04:04

NS8 protein

G8R

Reference  MKFLVFLGIITTVAAFHQECSLQSCTQHQPYVV
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Mutated    MKFLVFLRIITTVAAFHQECSLQSCTQHQPYVV

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DRB1*04:04 FLGIITTVAAFHQECSLQ FLRIITTVAAFHQECSLQ 651 177
HLA-DRB1*04:04 FLGIITTVAAFHQECSL FLRIITTVAAFHQECSL 135 40
HLA-DRB1*04:04 FLGIITTVAAFHQECS FLRIITTVAAFHQECS 157 48
HLA-DRB1*04:04 VFLGIITTVAAFHQECSL VFLRIITTVAAFHQECSL 361 120
HLA-DRB1*04:04 VFLGIITTVAAFHQECS VFLRIITTVAAFHQECS 80 27
HLA-DRB1*04:04 FLGIITTVAAFHQEC FLRIITTVAAFHQEC 65 24
HLA-DRB1*04:04 MKFLVFLGIITTVAAFHQEC MKFLVFLRIITTVAAFHQEC 244 91
HLA-DRB1*04:04 VFLGIITTVAAFHQEC VFLRIITTVAAFHQEC 95 36
HLA-DRB1*04:04 KFLVFLGIITTVAAFHQECS KFLVFLRIITTVAAFHQECS 230 88
HLA-DRB1*04:04 FLVFLGIITTVAAFHQECSL FLVFLRIITTVAAFHQECSL 242 93
HLA-DRB1*04:04 LGIITTVAAFHQECSLQ LRIITTVAAFHQECSLQ 281 108
HLA-DRB1*04:04 LGIITTVAAFHQECSL LRIITTVAAFHQECSL 332 130
HLA-DRB1*04:04 VFLGIITTVAAFHQECSLQ VFLRIITTVAAFHQECSLQ 245 98
HLA-DRB1*04:04 FLGIITTVAAFHQECSLQS FLRIITTVAAFHQECSLQS 346 140
HLA-DRB1*04:04 VFLGIITTVAAFHQECSLQS VFLRIITTVAAFHQECSLQS 227 93
HLA-DRB1*04:04 LVFLGIITTVAAFHQECSLQ LVFLRIITTVAAFHQECSLQ 246 101
HLA-DRB1*04:04 LVFLGIITTVAAFHQEC LVFLRIITTVAAFHQEC 73 30
HLA-DRB1*04:04 FLVFLGIITTVAAFHQEC FLVFLRIITTVAAFHQEC 318 133
HLA-DRB1*04:04 LVFLGIITTVAAFHQECS LVFLRIITTVAAFHQECS 332 139
HLA-DRB1*04:04 FLGIITTVAAFHQECSLQSC FLRIITTVAAFHQECSLQSC 303 128
HLA-DRB1*04:04 MKFLVFLGIITTVAAFH MKFLVFLRIITTVAAFH 99 42
HLA-DRB1*04:04 KFLVFLGIITTVAAFHQEC KFLVFLRIITTVAAFHQEC 234 101
HLA-DRB1*04:04 FLVFLGIITTVAAFHQECS FLVFLRIITTVAAFHQECS 236 102
HLA-DRB1*04:04 FLVFLGIITTVAAFHQE FLVFLRIITTVAAFHQE 64 28
HLA-DRB1*04:04 KFLVFLGIITTVAAFHQ KFLVFLRIITTVAAFHQ 66 29
HLA-DRB1*04:04 MKFLVFLGIITTVAAF MKFLVFLRIITTVAAF 261 115
HLA-DRB1*04:04 KFLVFLGIITTVAAFHQE KFLVFLRIITTVAAFHQE 273 121
HLA-DRB1*04:04 MKFLVFLGIITTVAAFHQ MKFLVFLRIITTVAAFHQ 281 126
HLA-DRB1*04:04 LVFLGIITTVAAFHQECSL LVFLRIITTVAAFHQECSL 240 109
HLA-DRB1*04:04 MKFLVFLGIITTVAAFHQE MKFLVFLRIITTVAAFHQE 200 91
HLA-DRB1*04:04 KFLVFLGIITTVAAFH KFLVFLRIITTVAAFH 130 60
HLA-DRB1*04:04 LGIITTVAAFHQECS LRIITTVAAFHQECS 116 54
HLA-DRB1*04:04 LVFLGIITTVAAFHQE LVFLRIITTVAAFHQE 85 41
HLA-DRB1*04:04 VFLGIITTVAAFHQE VFLRIITTVAAFHQE 37 18
HLA-DRB1*04:04 FLVFLGIITTVAAFHQ FLVFLRIITTVAAFHQ 87 43

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-DRB1*04:04 EIQLQAAVGELLLLEW EIQLQAAVNELLLLEW 780 340
HLA-DRB1*04:04 IQLQAAVGELLLLEW IQLQAAVNELLLLEW 705 308
HLA-DRB1*04:04 EIQLQAAVGELLLLE EIQLQAAVNELLLLE 408 198

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*04:04 STVFPPTSFGPLVRK STVFPLTSFGPLVRK 2558 198
HLA-DRB1*04:04 FSTVFPPTSFGPLVR FSTVFPLTSFGPLVR 2330 185
HLA-DRB1*04:04 FSTVFPPTSFGPLVRK FSTVFPLTSFGPLVRK 4113 374
HLA-DRB1*04:04 STVFPPTSFGPLVRKI STVFPLTSFGPLVRKI 3920 391
HLA-DRB1*04:04 FSTVFPPTSFGPLVRKI FSTVFPLTSFGPLVRKI 2707 288
HLA-DRB1*04:04 TVFPPTSFGPLVRKI TVFPLTSFGPLVRKI 1976 213
HLA-DRB1*04:04 STVFPPTSFGPLVRKIF STVFPLTSFGPLVRKIF 2325 291
HLA-DRB1*04:04 TVFPPTSFGPLVRKIF TVFPLTSFGPLVRKIF 2797 383
HLA-DRB1*04:04 VFPPTSFGPLVRKIF VFPLTSFGPLVRKIF 1333 217
HLA-DRB1*04:04 TVFPPTSFGPLVRKIFV TVFPLTSFGPLVRKIFV 2061 336
HLA-DRB1*04:04 LFSTVFPPTSFGPLVR LFSTVFPLTSFGPLVR 2413 395
HLA-DRB1*04:04 LFSTVFPPTSFGPLVRK LFSTVFPLTSFGPLVRK 1721 291
HLA-DRB1*04:04 VFPPTSFGPLVRKIFV VFPLTSFGPLVRKIFV 2456 421
HLA-DRB1*04:04 VFPPTSFGPLVRKIFVD VFPLTSFGPLVRKIFVD 2203 390
HLA-DRB1*04:04 FSTVFPPTSFGPLVRKIFV FSTVFPLTSFGPLVRKIFV 2549 477
HLA-DRB1*04:04 FSTVFPPTSFGPLVRKIFVD FSTVFPLTSFGPLVRKIFVD 1858 386
HLA-DRB1*04:04 STVFPPTSFGPLVRKIFVDG STVFPLTSFGPLVRKIFVDG 2058 438
HLA-DRB1*04:04 LFSTVFPPTSFGPLVRKIF LFSTVFPLTSFGPLVRKIF 2014 442
HLA-DRB1*04:04 FPPTSFGPLVRKIFV FPLTSFGPLVRKIFV 1301 291
HLA-DRB1*04:04 LFSTVFPPTSFGPLVRKIFV LFSTVFPLTSFGPLVRKIFV 1277 349
HLA-DRB1*04:04 LFSTVFPPTSFGPLV LFSTVFPLTSFGPLV 958 281
HLA-DRB1*04:04 VLFSTVFPPTSFGPLVRKI VLFSTVFPLTSFGPLVRKI 1412 444
HLA-DRB1*04:04 VLFSTVFPPTSFGPLVR VLFSTVFPLTSFGPLVR 922 294
HLA-DRB1*04:04 TVFPPTSFGPLVRKIFVDGV TVFPLTSFGPLVRKIFVDGV 1123 399
HLA-DRB1*04:04 VLFSTVFPPTSFGPLVRKIF VLFSTVFPLTSFGPLVRKIF 835 314
HLA-DRB1*04:04 NVLFSTVFPPTSFGPLVRK NVLFSTVFPLTSFGPLVRK 1054 422
HLA-DRB1*04:04 VFPPTSFGPLVRKIFVDGVP VFPLTSFGPLVRKIFVDGVP 767 362
HLA-DRB1*04:04 NVLFSTVFPPTSFGPLVRKI NVLFSTVFPLTSFGPLVRKI 617 299

NSP14 protein

P43L

Reference  LHPTQAPTHLSVDTKFKTEGLCVDIPGIPKDMTYRRLISMMGFKMNYQVNG
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Mutated    LHPTQAPTHLSVDTKFKTEGLCVDILGIPKDMTYRRLISMMGFKMNYQVNG

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DRB1*04:04 VDIPGIPKDMTYRRL VDILGIPKDMTYRRL 3285 496

NSP16 protein

R287I

Reference  LKEGQINDMILSLLSKGRLIIRENNRVVISSDVLVNN
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Mutated    LKEGQINDMILSLLSKGRLIIRENNIVVISSDVLVNN

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DRB1*04:04 IIRENNRVVISSDVL IIRENNIVVISSDVL 792 279
HLA-DRB1*04:04 IRENNRVVISSDVLV IRENNIVVISSDVLV 401 171
HLA-DRB1*04:04 IIRENNRVVISSDVLV IIRENNIVVISSDVLV 686 330