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*14:01 and peptides affected by the mutations

Weaker binding was not found, while stronger binding was found for 54 entries. There are 10 tight binders for the HLA-DRB1*14:01 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*14:01

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*14:01 MKFLVFLGIITTVAAFH MKFLVFLRIITTVAAFH 732 350
HLA-DRB1*14:01 LVFLGIITTVAAFHQEC LVFLRIITTVAAFHQEC 689 340
HLA-DRB1*14:01 MKFLVFLGIITTVAA MKFLVFLRIITTVAA 707 349
HLA-DRB1*14:01 VFLGIITTVAAFHQECS VFLRIITTVAAFHQECS 702 347
HLA-DRB1*14:01 FLVFLGIITTVAAFHQE FLVFLRIITTVAAFHQE 570 282
HLA-DRB1*14:01 KFLVFLGIITTVAAFHQ KFLVFLRIITTVAAFHQ 555 275

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*14:01 TVFPPTSFGPLVRKI TVFPLTSFGPLVRKI 2669 333
HLA-DRB1*14:01 STVFPPTSFGPLVRK STVFPLTSFGPLVRK 3007 392
HLA-DRB1*14:01 FSTVFPPTSFGPLVR FSTVFPLTSFGPLVR 2885 482
HLA-DRB1*14:01 HCANFNVLFSTVFPP HCANFNVLFSTVFPL 759 186
HLA-DRB1*14:01 STVFPPTSFGPLVRKIF STVFPLTSFGPLVRKIF 1597 397
HLA-DRB1*14:01 NVLFSTVFPPTSFGPLVRKI NVLFSTVFPLTSFGPLVRKI 1585 429
HLA-DRB1*14:01 VFPPTSFGPLVRKIF VFPLTSFGPLVRKIF 844 233
HLA-DRB1*14:01 CANFNVLFSTVFPPT CANFNVLFSTVFPLT 473 134
HLA-DRB1*14:01 NVLFSTVFPPTSFGP NVLFSTVFPLTSFGP 751 216
HLA-DRB1*14:01 ANFNVLFSTVFPPTS ANFNVLFSTVFPLTS 386 114
HLA-DRB1*14:01 CANFNVLFSTVFPPTS CANFNVLFSTVFPLTS 1044 314
HLA-DRB1*14:01 HCANFNVLFSTVFPPTS HCANFNVLFSTVFPLTS 783 248
HLA-DRB1*14:01 HCANFNVLFSTVFPPT HCANFNVLFSTVFPLT 1209 384
HLA-DRB1*14:01 TVFPPTSFGPLVRKIFV TVFPLTSFGPLVRKIFV 1121 361
HLA-DRB1*14:01 STVFPPTSFGPLVRKIFVDG STVFPLTSFGPLVRKIFVDG 1419 457
HLA-DRB1*14:01 VLFSTVFPPTSFGPLVRKIF VLFSTVFPLTSFGPLVRKIF 1231 412
HLA-DRB1*14:01 FSTVFPPTSFGPLVRKIFVD FSTVFPLTSFGPLVRKIFVD 1252 420
HLA-DRB1*14:01 LHCANFNVLFSTVFPPT LHCANFNVLFSTVFPLT 881 306
HLA-DRB1*14:01 NFNVLFSTVFPPTSF NFNVLFSTVFPLTSF 330 116
HLA-DRB1*14:01 VFPPTSFGPLVRKIFV VFPLTSFGPLVRKIFV 1350 479
HLA-DRB1*14:01 VFPPTSFGPLVRKIFVD VFPLTSFGPLVRKIFVD 1204 429
HLA-DRB1*14:01 LFSTVFPPTSFGPLVRKIFV LFSTVFPLTSFGPLVRKIFV 1094 396
HLA-DRB1*14:01 NFNVLFSTVFPPTSFGP NFNVLFSTVFPLTSFGP 728 273
HLA-DRB1*14:01 FNVLFSTVFPPTSFG FNVLFSTVFPLTSFG 432 165
HLA-DRB1*14:01 ILHCANFNVLFSTVFPP ILHCANFNVLFSTVFPL 1057 411
HLA-DRB1*14:01 FNVLFSTVFPPTSFGPLVRK FNVLFSTVFPLTSFGPLVRK 1186 467
HLA-DRB1*14:01 ANFNVLFSTVFPPTSFG ANFNVLFSTVFPLTSFG 653 258
HLA-DRB1*14:01 FPPTSFGPLVRKIFV FPLTSFGPLVRKIFV 608 242
HLA-DRB1*14:01 CANFNVLFSTVFPPTSF CANFNVLFSTVFPLTSF 618 247
HLA-DRB1*14:01 NFNVLFSTVFPPTSFG NFNVLFSTVFPLTSFG 900 360
HLA-DRB1*14:01 TVFPPTSFGPLVRKIFVDGV TVFPLTSFGPLVRKIFVDGV 1160 465
HLA-DRB1*14:01 ANFNVLFSTVFPPTSF ANFNVLFSTVFPLTSF 812 327
HLA-DRB1*14:01 FNVLFSTVFPPTSFGPL FNVLFSTVFPLTSFGPL 944 381
HLA-DRB1*14:01 VLFSTVFPPTSFGPL VLFSTVFPLTSFGPL 1226 495
HLA-DRB1*14:01 ILHCANFNVLFSTVFPPTS ILHCANFNVLFSTVFPLTS 1031 445
HLA-DRB1*14:01 NFNVLFSTVFPPTSFGPLVR NFNVLFSTVFPLTSFGPLVR 976 448
HLA-DRB1*14:01 PPTSFGPLVRKIFVD PLTSFGPLVRKIFVD 772 355

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*14:01 VDIPGIPKDMTYRRL VDILGIPKDMTYRRL 3537 475

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*14:01 IGNPKAIKCVPQADV IGNPKAIKCVPQAYV 1272 478
HLA-DRB1*14:01 HDIGNPKAIKCVPQADVEWK HDIGNPKAIKCVPQAYVEWK 1235 475
HLA-DRB1*14:01 NPKAIKCVPQADVEWKFYDA NPKAIKCVPQAYVEWKFYDA 1273 492
HLA-DRB1*14:01 DIGNPKAIKCVPQADVEWKF DIGNPKAIKCVPQAYVEWKF 1187 463
HLA-DRB1*14:01 GNPKAIKCVPQADVEWKFYD GNPKAIKCVPQAYVEWKFYD 1208 481
HLA-DRB1*14:01 GNPKAIKCVPQADVE GNPKAIKCVPQAYVE 1054 426
HLA-DRB1*14:01 IGNPKAIKCVPQADVEWKFY IGNPKAIKCVPQAYVEWKFY 1154 468
HLA-DRB1*14:01 KAIKCVPQADVEWKF KAIKCVPQAYVEWKF 773 316
HLA-DRB1*14:01 NPKAIKCVPQADVEW NPKAIKCVPQAYVEW 826 348
HLA-DRB1*14:01 PKAIKCVPQADVEWK PKAIKCVPQAYVEWK 712 307