Summary

This strain contains 23 protein-level mutations:

  • 12 mutations in Spike protein: L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I, V1176F
  • 2 mutations in N protein: P80R, 203-204 RG->KR
  • 1 mutation in NS3 protein: S253P
  • 1 mutation in NS8 protein: E92K
  • 1 mutation in NS9b protein: Q77E
  • 1 mutation in NS9c protein: 49-50 VG->LN
  • 2 mutations in NSP3 protein: S370L, K977Q
  • 1 mutation in NSP6 protein: SGF 106-108 deletion
  • 1 mutation in NSP12 protein: P323L
  • 1 mutation in NSP13 protein: E341D

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-DQA1*01:03/DQB1*06:09 and peptides affected by the mutations

Weaker binding was found for 41 epitopes, while stronger binding was found for 54 entries. There are 4 tight binders for the HLA-DQA1*01:03/DQB1*06:09 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-DQA1*01:03/DQB1*06:09

NS3 protein

S253P

Reference  VTFFIYNKIVDEPEEHVQIHTIDGSSGVVNPVMEPIYDEPTTTTSVPL
           ||||||||||||||||||||||||| ||||||||||||||||||||||
Mutated    VTFFIYNKIVDEPEEHVQIHTIDGSPGVVNPVMEPIYDEPTTTTSVPL

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DQA1*01:03/DQB1*06:09 IHTIDGSSGVVNPVM IHTIDGSPGVVNPVM 484 1072
HLA-DQA1*01:03/DQB1*06:09 HTIDGSSGVVNPVMEPIYDE HTIDGSPGVVNPVMEPIYDE 411 868
HLA-DQA1*01:03/DQB1*06:09 IHTIDGSSGVVNPVMEPIY IHTIDGSPGVVNPVMEPIY 496 1036
HLA-DQA1*01:03/DQB1*06:09 TIDGSSGVVNPVMEPIYDEP TIDGSPGVVNPVMEPIYDEP 458 954

NSP6 protein

SGF 106-108 deletion

Reference  FNMVYMPASWVMRIMTWLDMVDTSLSGFKLKDCVMYASAVVLLILMTARTVYD
           |||||||||||||||||||||||||   |||||||||||||||||||||||||
Mutated    FNMVYMPASWVMRIMTWLDMVDTSL‑‑‑KLKDCVMYASAVVLLILMTARTVYD

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DQA1*01:03/DQB1*06:09 FKLKDCVMYASAVVLLI - 210 -
HLA-DQA1*01:03/DQB1*06:09 FKLKDCVMYASAVVLL - 212 -
HLA-DQA1*01:03/DQB1*06:09 FKLKDCVMYASAVVL KLKDCVMYASAVVL 219 -
HLA-DQA1*01:03/DQB1*06:09 GFKLKDCVMYASAVVLL - 233 -
HLA-DQA1*01:03/DQB1*06:09 DTSLSGFKLKDCVMYASAVVLLI DTSLKLKDCVMYASAVVLLI - 243
HLA-DQA1*01:03/DQB1*06:09 SGFKLKDCVMYASAVVLLIL - 248 -
HLA-DQA1*01:03/DQB1*06:09 TSLSGFKLKDCVMYASAVVLLIL TSLKLKDCVMYASAVVLLIL - 251
HLA-DQA1*01:03/DQB1*06:09 MRIMTWLDMVDTSLS MRIMTWLDMVDTSL 253 -
HLA-DQA1*01:03/DQB1*06:09 GFKLKDCVMYASAVVL KLKDCVMYASAVVL 253 -
HLA-DQA1*01:03/DQB1*06:09 VDTSLSGFKLKDCVMYASAVVLL VDTSLKLKDCVMYASAVVLL - 260
HLA-DQA1*01:03/DQB1*06:09 GFKLKDCVMYASAVVLLILM - 262 -
HLA-DQA1*01:03/DQB1*06:09 SLSGFKLKDCVMYASAVVLLILM SLKLKDCVMYASAVVLLILM - 264
HLA-DQA1*01:03/DQB1*06:09 SGFKLKDCVMYASAVVLLI - 281 -
HLA-DQA1*01:03/DQB1*06:09 GFKLKDCVMYASAVVLLIL - 281 -
HLA-DQA1*01:03/DQB1*06:09 FKLKDCVMYASAVVLLILMT - 281 -
HLA-DQA1*01:03/DQB1*06:09 TSLSGFKLKDCVMYASAVVLLI TSLKLKDCVMYASAVVLLI - 282
HLA-DQA1*01:03/DQB1*06:09 SLSGFKLKDCVMYASAVVLLIL SLKLKDCVMYASAVVLLIL - 282
HLA-DQA1*01:03/DQB1*06:09 VMRIMTWLDMVDTSLS - 283 -
HLA-DQA1*01:03/DQB1*06:09 LSGFKLKDCVMYASAVVLLILMT LKLKDCVMYASAVVLLILMT - 286
HLA-DQA1*01:03/DQB1*06:09 SGFKLKDCVMYASAVVL KLKDCVMYASAVVL 293 -
HLA-DQA1*01:03/DQB1*06:09 FKLKDCVMYASAVVLLILM - 293 -
HLA-DQA1*01:03/DQB1*06:09 LSGFKLKDCVMYASAVVLLILM LKLKDCVMYASAVVLLILM - 298
HLA-DQA1*01:03/DQB1*06:09 WVMRIMTWLDMVDTSLS - 302 -
HLA-DQA1*01:03/DQB1*06:09 DTSLSGFKLKDCVMYASAVVLL DTSLKLKDCVMYASAVVLL - 303
HLA-DQA1*01:03/DQB1*06:09 MVDTSLSGFKLKDCVMYASAVVL MVDTSLKLKDCVMYASAVVL - 305
HLA-DQA1*01:03/DQB1*06:09 GFKLKDCVMYASAVV KLKDCVMYASAVV 325 -
HLA-DQA1*01:03/DQB1*06:09 SWVMRIMTWLDMVDTSLSGFKLK SWVMRIMTWLDMVDTSLKLK - 334
HLA-DQA1*01:03/DQB1*06:09 MRIMTWLDMVDTSLSG MRIMTWLDMVDTSL 337 -
HLA-DQA1*01:03/DQB1*06:09 RIMTWLDMVDTSLSG RIMTWLDMVDTSL 339 -
HLA-DQA1*01:03/DQB1*06:09 VMRIMTWLDMVDTSLSG - 346 -
HLA-DQA1*01:03/DQB1*06:09 PASWVMRIMTWLDMVDTSLS - 352 -
HLA-DQA1*01:03/DQB1*06:09 SGFKLKDCVMYASAVV KLKDCVMYASAVV 354 -
HLA-DQA1*01:03/DQB1*06:09 ASWVMRIMTWLDMVDTSLSGFKL ASWVMRIMTWLDMVDTSLKL - 355
HLA-DQA1*01:03/DQB1*06:09 SWVMRIMTWLDMVDTSLSGF - 356 -
HLA-DQA1*01:03/DQB1*06:09 WVMRIMTWLDMVDTSLSGFKLKD WVMRIMTWLDMVDTSLKLKD - 357
HLA-DQA1*01:03/DQB1*06:09 PASWVMRIMTWLDMVDTSLSGFK PASWVMRIMTWLDMVDTSLK - 360
HLA-DQA1*01:03/DQB1*06:09 ASWVMRIMTWLDMVDTSLSG - 368 -
HLA-DQA1*01:03/DQB1*06:09 MRIMTWLDMVDTSLSGF MRIMTWLDMVDTSL 370 -
HLA-DQA1*01:03/DQB1*06:09 WVMRIMTWLDMVDTSLSGFKLK WVMRIMTWLDMVDTSLKLK - 371
HLA-DQA1*01:03/DQB1*06:09 VDTSLSGFKLKDCVMYASAVVL VDTSLKLKDCVMYASAVVL - 371
HLA-DQA1*01:03/DQB1*06:09 RIMTWLDMVDTSLSGF RIMTWLDMVDTSL 380 -
HLA-DQA1*01:03/DQB1*06:09 ASWVMRIMTWLDMVDTSLSGFK ASWVMRIMTWLDMVDTSLK - 382
HLA-DQA1*01:03/DQB1*06:09 VMRIMTWLDMVDTSLSGFKLKDC VMRIMTWLDMVDTSLKLKDC - 387
HLA-DQA1*01:03/DQB1*06:09 ASWVMRIMTWLDMVDTSLS - 389 -
HLA-DQA1*01:03/DQB1*06:09 SWVMRIMTWLDMVDTSLSGFKL SWVMRIMTWLDMVDTSLKL - 389
HLA-DQA1*01:03/DQB1*06:09 GFKLKDCVMYASAVVLLI - 395 -
HLA-DQA1*01:03/DQB1*06:09 FKLKDCVMYASAVVLLIL - 401 -
HLA-DQA1*01:03/DQB1*06:09 VMRIMTWLDMVDTSLSGFKLKD VMRIMTWLDMVDTSLKLKD - 403
HLA-DQA1*01:03/DQB1*06:09 SLSGFKLKDCVMYASAVVLLI SLKLKDCVMYASAVVLLI - 403
HLA-DQA1*01:03/DQB1*06:09 SWVMRIMTWLDMVDTSLSG - 408 -
HLA-DQA1*01:03/DQB1*06:09 WVMRIMTWLDMVDTSLSGF - 408 -
HLA-DQA1*01:03/DQB1*06:09 LSGFKLKDCVMYASAVV LKLKDCVMYASAVV 410 -
HLA-DQA1*01:03/DQB1*06:09 LSGFKLKDCVMYASAVVLLIL LKLKDCVMYASAVVLLIL - 410
HLA-DQA1*01:03/DQB1*06:09 MRIMTWLDMVDTSLSGFKLKDCV MRIMTWLDMVDTSLKLKDCV - 419
HLA-DQA1*01:03/DQB1*06:09 DMVDTSLSGFKLKDCVMYASAVV DMVDTSLKLKDCVMYASAVV - 424
HLA-DQA1*01:03/DQB1*06:09 RIMTWLDMVDTSLSGFK RIMTWLDMVDTSLK 426 -
HLA-DQA1*01:03/DQB1*06:09 SGFKLKDCVMYASAVVLL - 429 -
HLA-DQA1*01:03/DQB1*06:09 TSLSGFKLKDCVMYASAVVLL TSLKLKDCVMYASAVVLL - 441
HLA-DQA1*01:03/DQB1*06:09 IMTWLDMVDTSLSGF IMTWLDMVDTSL 442 -
HLA-DQA1*01:03/DQB1*06:09 MRIMTWLDMVDTSLSGFKLKDC MRIMTWLDMVDTSLKLKDC - 463
HLA-DQA1*01:03/DQB1*06:09 MTWLDMVDTSLSGFK MTWLDMVDTSLK 467 -
HLA-DQA1*01:03/DQB1*06:09 IMTWLDMVDTSLSGFK IMTWLDMVDTSLK 484 -
HLA-DQA1*01:03/DQB1*06:09 RIMTWLDMVDTSLSGFKLKDCVM RIMTWLDMVDTSLKLKDCVM - 495
HLA-DQA1*01:03/DQB1*06:09 TWLDMVDTSLSGFKL TWLDMVDTSLKL 498 -
HLA-DQA1*01:03/DQB1*06:09 MRIMTWLDMVDTSLSGFK MRIMTWLDMVDTSLK 628 272
HLA-DQA1*01:03/DQB1*06:09 LSGFKLKDCVMYASAVVL LKLKDCVMYASAVVL 513 226
HLA-DQA1*01:03/DQB1*06:09 RIMTWLDMVDTSLSGFKL RIMTWLDMVDTSLKL 744 332

NSP12 protein

P323L

Reference  CVNCLDDRCILHCANFNVLFSTVFPPTSFGPLVRKIFVDGVPFVVSTGYHF
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    CVNCLDDRCILHCANFNVLFSTVFPLTSFGPLVRKIFVDGVPFVVSTGYHF

Export table to csv 
Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DQA1*01:03/DQB1*06:09 STVFPPTSFGPLVRK STVFPLTSFGPLVRK 1893 434
HLA-DQA1*01:03/DQB1*06:09 STVFPPTSFGPLVRKI STVFPLTSFGPLVRKI 1596 369
HLA-DQA1*01:03/DQB1*06:09 TVFPPTSFGPLVRKI TVFPLTSFGPLVRKI 1474 353
HLA-DQA1*01:03/DQB1*06:09 TVFPPTSFGPLVRKIF TVFPLTSFGPLVRKIF 1352 345
HLA-DQA1*01:03/DQB1*06:09 STVFPPTSFGPLVRKIF STVFPLTSFGPLVRKIF 1451 378
HLA-DQA1*01:03/DQB1*06:09 TVFPPTSFGPLVRKIFV TVFPLTSFGPLVRKIFV 1393 389
HLA-DQA1*01:03/DQB1*06:09 STVFPPTSFGPLVRKIFVD STVFPLTSFGPLVRKIFVD 1470 426
HLA-DQA1*01:03/DQB1*06:09 VFPPTSFGPLVRKIF VFPLTSFGPLVRKIF 1219 356
HLA-DQA1*01:03/DQB1*06:09 FSTVFPPTSFGPLVR FSTVFPLTSFGPLVR 1257 373
HLA-DQA1*01:03/DQB1*06:09 TVFPPTSFGPLVRKIFVDG TVFPLTSFGPLVRKIFVDG 1580 479
HLA-DQA1*01:03/DQB1*06:09 VFPPTSFGPLVRKIFV VFPLTSFGPLVRKIFV 1285 392
HLA-DQA1*01:03/DQB1*06:09 FSTVFPPTSFGPLVRKI FSTVFPLTSFGPLVRKI 1178 361
HLA-DQA1*01:03/DQB1*06:09 VFPPTSFGPLVRKIFVD VFPLTSFGPLVRKIFVD 1499 463
HLA-DQA1*01:03/DQB1*06:09 FSTVFPPTSFGPLVRK FSTVFPLTSFGPLVRK 1285 402
HLA-DQA1*01:03/DQB1*06:09 STVFPPTSFGPLVRKIFVDG STVFPLTSFGPLVRKIFVDG 1125 352
HLA-DQA1*01:03/DQB1*06:09 FSTVFPPTSFGPLVRKIFV FSTVFPLTSFGPLVRKIFV 1080 372
HLA-DQA1*01:03/DQB1*06:09 FPPTSFGPLVRKIFV FPLTSFGPLVRKIFV 1237 438
HLA-DQA1*01:03/DQB1*06:09 FSTVFPPTSFGPLVRKIFVD FSTVFPLTSFGPLVRKIFVD 807 303
HLA-DQA1*01:03/DQB1*06:09 TVFPPTSFGPLVRKIFVDGV TVFPLTSFGPLVRKIFVDGV 804 331
HLA-DQA1*01:03/DQB1*06:09 VFPPTSFGPLVRKIFVDGV VFPLTSFGPLVRKIFVDGV 1133 492
HLA-DQA1*01:03/DQB1*06:09 LFSTVFPPTSFGPLVRK LFSTVFPLTSFGPLVRK 842 389
HLA-DQA1*01:03/DQB1*06:09 LFSTVFPPTSFGPLVRKIF LFSTVFPLTSFGPLVRKIF 767 357
HLA-DQA1*01:03/DQB1*06:09 VFPPTSFGPLVRKIFVDGVP VFPLTSFGPLVRKIFVDGVP 747 349
HLA-DQA1*01:03/DQB1*06:09 LFSTVFPPTSFGPLVR LFSTVFPLTSFGPLVR 803 398