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*14:04 and peptides affected by the mutations

Weaker binding was not found, while stronger binding was found for 55 entries. There is 1 tight binder for the HLA-DRB1*14:04 in the reference immunopeptidome (IC50 affinity ≤ 50 nM); 0 of them became non-tight binders (0.0%) and 0 novel tight binders appeared (0.0%). To avoid possible divisions by zero, we used + 1 regularization term in denominators when calculating percentages.

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HLA-DRB1*14:04

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*14:04 TVFPPTSFGPLVRKI TVFPLTSFGPLVRKI 2683 337
HLA-DRB1*14:04 STVFPPTSFGPLVRK STVFPLTSFGPLVRK 2772 368
HLA-DRB1*14:04 FSTVFPPTSFGPLVRKI FSTVFPLTSFGPLVRKI 3137 496
HLA-DRB1*14:04 FSTVFPPTSFGPLVR FSTVFPLTSFGPLVR 2612 418
HLA-DRB1*14:04 STVFPPTSFGPLVRKIF STVFPLTSFGPLVRKIF 1803 412
HLA-DRB1*14:04 VFPPTSFGPLVRKIF VFPLTSFGPLVRKIF 1015 264
HLA-DRB1*14:04 NVLFSTVFPPTSFGPLVRKI NVLFSTVFPLTSFGPLVRKI 1200 350
HLA-DRB1*14:04 STVFPPTSFGPLVRKIFVDG STVFPLTSFGPLVRKIFVDG 1634 478
HLA-DRB1*14:04 FSTVFPPTSFGPLVRKIFVD FSTVFPLTSFGPLVRKIFVD 1465 431
HLA-DRB1*14:04 HCANFNVLFSTVFPP HCANFNVLFSTVFPL 584 175
HLA-DRB1*14:04 NVLFSTVFPPTSFGPLVRK NVLFSTVFPLTSFGPLVRK 1498 452
HLA-DRB1*14:04 TVFPPTSFGPLVRKIFV TVFPLTSFGPLVRKIFV 1368 421
HLA-DRB1*14:04 LFSTVFPPTSFGPLVRKIFV LFSTVFPLTSFGPLVRKIFV 1255 394
HLA-DRB1*14:04 VLFSTVFPPTSFGPLVRKIF VLFSTVFPLTSFGPLVRKIF 1183 380
HLA-DRB1*14:04 VFPPTSFGPLVRKIFVD VFPLTSFGPLVRKIFVD 1472 481
HLA-DRB1*14:04 NVLFSTVFPPTSFGP NVLFSTVFPLTSFGP 612 202
HLA-DRB1*14:04 CANFNVLFSTVFPPT CANFNVLFSTVFPLT 383 128
HLA-DRB1*14:04 NVLFSTVFPPTSFGPLV NVLFSTVFPLTSFGPLV 1177 406
HLA-DRB1*14:04 CANFNVLFSTVFPPTS CANFNVLFSTVFPLTS 738 259
HLA-DRB1*14:04 ANFNVLFSTVFPPTS ANFNVLFSTVFPLTS 315 111
HLA-DRB1*14:04 LHCANFNVLFSTVFPP LHCANFNVLFSTVFPL 1211 431
HLA-DRB1*14:04 NVLFSTVFPPTSFGPL NVLFSTVFPLTSFGPL 1369 493
HLA-DRB1*14:04 HCANFNVLFSTVFPPTS HCANFNVLFSTVFPLTS 590 215
HLA-DRB1*14:04 HCANFNVLFSTVFPPT HCANFNVLFSTVFPLT 852 316
HLA-DRB1*14:04 LHCANFNVLFSTVFPPT LHCANFNVLFSTVFPLT 685 264
HLA-DRB1*14:04 FPPTSFGPLVRKIFV FPLTSFGPLVRKIFV 795 310
HLA-DRB1*14:04 NFNVLFSTVFPPTSFGP NFNVLFSTVFPLTSFGP 585 240
HLA-DRB1*14:04 ILHCANFNVLFSTVFPP ILHCANFNVLFSTVFPL 879 361
HLA-DRB1*14:04 FNVLFSTVFPPTSFGPL FNVLFSTVFPLTSFGPL 763 318
HLA-DRB1*14:04 NFNVLFSTVFPPTSF NFNVLFSTVFPLTSF 281 118
HLA-DRB1*14:04 FNVLFSTVFPPTSFGPLVRK FNVLFSTVFPLTSFGPLVRK 901 385
HLA-DRB1*14:04 VLFSTVFPPTSFGPL VLFSTVFPLTSFGPL 955 412
HLA-DRB1*14:04 TVFPPTSFGPLVRKIFVDGV TVFPLTSFGPLVRKIFVDGV 1027 449
HLA-DRB1*14:04 CANFNVLFSTVFPPTSF CANFNVLFSTVFPLTSF 500 220
HLA-DRB1*14:04 FNVLFSTVFPPTSFGP FNVLFSTVFPLTSFGP 893 412
HLA-DRB1*14:04 FNVLFSTVFPPTSFGPLVR FNVLFSTVFPLTSFGPLVR 1064 493
HLA-DRB1*14:04 NFNVLFSTVFPPTSFG NFNVLFSTVFPLTSFG 665 313
HLA-DRB1*14:04 ANFNVLFSTVFPPTSFG ANFNVLFSTVFPLTSFG 501 236
HLA-DRB1*14:04 VFPPTSFGPLVRKIFVDGVP VFPLTSFGPLVRKIFVDGVP 994 469
HLA-DRB1*14:04 ILHCANFNVLFSTVFPPTS ILHCANFNVLFSTVFPLTS 789 376
HLA-DRB1*14:04 ANFNVLFSTVFPPTSF ANFNVLFSTVFPLTSF 589 282
HLA-DRB1*14:04 FNVLFSTVFPPTSFG FNVLFSTVFPLTSFG 361 173

NSP14 protein

D345Y

Reference  ALLADKFPVLHDIGNPKAIKCVPQADVEWKFYDAQPCSDKAYKIEELFYSY
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Mutated    ALLADKFPVLHDIGNPKAIKCVPQAYVEWKFYDAQPCSDKAYKIEELFYSY

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DRB1*14:04 DIGNPKAIKCVPQADVEWKF DIGNPKAIKCVPQAYVEWKF 1177 478
HLA-DRB1*14:04 NPKAIKCVPQADVEWKFYDA NPKAIKCVPQAYVEWKFYDA 1210 497
HLA-DRB1*14:04 GNPKAIKCVPQADVEWKFYD GNPKAIKCVPQAYVEWKFYD 1177 493
HLA-DRB1*14:04 IGNPKAIKCVPQADVEWKFY IGNPKAIKCVPQAYVEWKFY 1141 481
HLA-DRB1*14:04 IGNPKAIKCVPQADV IGNPKAIKCVPQAYV 1138 489
HLA-DRB1*14:04 GNPKAIKCVPQADVE GNPKAIKCVPQAYVE 1034 445
HLA-DRB1*14:04 NPKAIKCVPQADVEW NPKAIKCVPQAYVEW 833 372
HLA-DRB1*14:04 KAIKCVPQADVEWKF KAIKCVPQAYVEWKF 779 354
HLA-DRB1*14:04 PKAIKCVPQADVEWK PKAIKCVPQAYVEWK 735 335

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*14:04 IIRENNRVVISSDVL IIRENNIVVISSDVL 571 214
HLA-DRB1*14:04 LIIRENNRVVISSDVL LIIRENNIVVISSDVL 553 252
HLA-DRB1*14:04 GRLIIRENNRVVISSDVL GRLIIRENNIVVISSDVL 797 380
HLA-DRB1*14:04 RLIIRENNRVVISSDVL RLIIRENNIVVISSDVL 347 172