Summary

This strain contains 26 protein-level mutations:

  • 9 mutations in Spike protein: T95I, 144-145 YY->SN, R346K, E484K, N501Y, D614G, Q677H, P681H, D950N
  • 2 mutations in N protein: T205I, Q241K
  • 1 mutation in NS3 protein: Q57H
  • 3 mutations in NS8 protein: T11K, P38S, S67F
  • 1 mutation in NS9b protein: R32L
  • 1 mutation in NS9c protein: L52F
  • 3 mutations in NSP3 protein: T237A, T720I, E997K
  • 1 mutation in NSP4 protein: T492I
  • 1 mutation in NSP6 protein: Q160R
  • 1 mutation in NSP12 protein: P323L
  • 2 mutations in NSP13 protein: P419S, L581F
  • 1 mutation in NSP14 protein: V125F

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*06:02 and peptides affected by the mutations

Weaker binding was found for 1 epitope, while stronger binding was found for 119 entries. There are 103 tight binders for the HLA-DQA1*01:03/DQB1*06:02 in the reference immunopeptidome (IC50 affinity ≤ 50 nM); 0 of them became non-tight binders (0.0%) and 3 novel tight binders appeared (2.9%). 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*06:02

Spike protein

T95I

Reference  VSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIV
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    VSGTNGTKRFDNPVLPFNDGVYFASIEKSNIIRGWIFGTTLDSKTQSLLIV

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DQA1*01:03/DQB1*06:02 NDGVYFASTEKSNII NDGVYFASIEKSNII 774 261
HLA-DQA1*01:03/DQB1*06:02 DGVYFASTEKSNIIRG DGVYFASIEKSNIIRG 898 304
HLA-DQA1*01:03/DQB1*06:02 NDGVYFASTEKSNIIRG NDGVYFASIEKSNIIRG 946 330
HLA-DQA1*01:03/DQB1*06:02 FNDGVYFASTEKSNI FNDGVYFASIEKSNI 832 293
HLA-DQA1*01:03/DQB1*06:02 GVYFASTEKSNIIRG GVYFASIEKSNIIRG 825 291
HLA-DQA1*01:03/DQB1*06:02 PFNDGVYFASTEKSNI PFNDGVYFASIEKSNI 1021 364
HLA-DQA1*01:03/DQB1*06:02 NDGVYFASTEKSNIIR NDGVYFASIEKSNIIR 904 325
HLA-DQA1*01:03/DQB1*06:02 DGVYFASTEKSNIIR DGVYFASIEKSNIIR 880 318
HLA-DQA1*01:03/DQB1*06:02 GVYFASTEKSNIIRGW GVYFASIEKSNIIRGW 820 298
HLA-DQA1*01:03/DQB1*06:02 PFNDGVYFASTEKSNIIRG PFNDGVYFASIEKSNIIRG 1115 406
HLA-DQA1*01:03/DQB1*06:02 FNDGVYFASTEKSNII FNDGVYFASIEKSNII 820 300
HLA-DQA1*01:03/DQB1*06:02 PFNDGVYFASTEKSN PFNDGVYFASIEKSN 1049 399
HLA-DQA1*01:03/DQB1*06:02 VYFASTEKSNIIRGW VYFASIEKSNIIRGW 898 343
HLA-DQA1*01:03/DQB1*06:02 LPFNDGVYFASTEKSNI LPFNDGVYFASIEKSNI 1085 418
HLA-DQA1*01:03/DQB1*06:02 DGVYFASTEKSNIIRGW DGVYFASIEKSNIIRGW 890 343
HLA-DQA1*01:03/DQB1*06:02 FNDGVYFASTEKSNIIRGW FNDGVYFASIEKSNIIRGW 949 368
HLA-DQA1*01:03/DQB1*06:02 PFNDGVYFASTEKSNII PFNDGVYFASIEKSNII 921 358
HLA-DQA1*01:03/DQB1*06:02 FNDGVYFASTEKSNIIR FNDGVYFASIEKSNIIR 913 355
HLA-DQA1*01:03/DQB1*06:02 FNDGVYFASTEKSNIIRGWI FNDGVYFASIEKSNIIRGWI 536 211
HLA-DQA1*01:03/DQB1*06:02 VYFASTEKSNIIRGWI VYFASIEKSNIIRGWI 787 314
HLA-DQA1*01:03/DQB1*06:02 NDGVYFASTEKSNIIRGWI NDGVYFASIEKSNIIRGWI 865 346
HLA-DQA1*01:03/DQB1*06:02 LPFNDGVYFASTEKSN LPFNDGVYFASIEKSN 1205 485
HLA-DQA1*01:03/DQB1*06:02 LPFNDGVYFASTEKSNIIRG LPFNDGVYFASIEKSNIIRG 696 282
HLA-DQA1*01:03/DQB1*06:02 GVYFASTEKSNIIRGWI GVYFASIEKSNIIRGWI 828 336
HLA-DQA1*01:03/DQB1*06:02 PFNDGVYFASTEKSNIIRGW PFNDGVYFASIEKSNIIRGW 611 248
HLA-DQA1*01:03/DQB1*06:02 NDGVYFASTEKSNIIRGWIF NDGVYFASIEKSNIIRGWIF 472 198
HLA-DQA1*01:03/DQB1*06:02 DGVYFASTEKSNIIRGWIFG DGVYFASIEKSNIIRGWIFG 528 224
HLA-DQA1*01:03/DQB1*06:02 YFASTEKSNIIRGWI YFASIEKSNIIRGWI 749 324
HLA-DQA1*01:03/DQB1*06:02 YFASTEKSNIIRGWIF YFASIEKSNIIRGWIF 603 270
HLA-DQA1*01:03/DQB1*06:02 NPVLPFNDGVYFASTEKSNI NPVLPFNDGVYFASIEKSNI 953 431
HLA-DQA1*01:03/DQB1*06:02 FASTEKSNIIRGWIFG FASIEKSNIIRGWIFG 645 293
HLA-DQA1*01:03/DQB1*06:02 GVYFASTEKSNIIRGWIFGT GVYFASIEKSNIIRGWIFGT 565 258
HLA-DQA1*01:03/DQB1*06:02 DGVYFASTEKSNIIRGWIF DGVYFASIEKSNIIRGWIF 747 344
HLA-DQA1*01:03/DQB1*06:02 FASTEKSNIIRGWIF FASIEKSNIIRGWIF 521 246
HLA-DQA1*01:03/DQB1*06:02 VYFASTEKSNIIRGWIF VYFASIEKSNIIRGWIF 719 345
HLA-DQA1*01:03/DQB1*06:02 YFASTEKSNIIRGWIFG YFASIEKSNIIRGWIFG 797 390
HLA-DQA1*01:03/DQB1*06:02 PVLPFNDGVYFASTEKSNII PVLPFNDGVYFASIEKSNII 765 375
HLA-DQA1*01:03/DQB1*06:02 GVYFASTEKSNIIRGWIFG GVYFASIEKSNIIRGWIFG 822 403

D614G

Reference  PCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTG
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    PCSFGGVSVITPGTNTSNQVAVLYQGVNCTEVPVAIHADQLTPTWRVYSTG

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DQA1*01:03/DQB1*06:02 GTNTSNQVAVLYQDVN GTNTSNQVAVLYQGVN 413 170
HLA-DQA1*01:03/DQB1*06:02 SNQVAVLYQDVNCTE SNQVAVLYQGVNCTE 960 408
HLA-DQA1*01:03/DQB1*06:02 TNTSNQVAVLYQDVN TNTSNQVAVLYQGVN 292 126
HLA-DQA1*01:03/DQB1*06:02 NTSNQVAVLYQDVNC NTSNQVAVLYQGVNC 417 181
HLA-DQA1*01:03/DQB1*06:02 GTNTSNQVAVLYQDV GTNTSNQVAVLYQGV 312 136
HLA-DQA1*01:03/DQB1*06:02 PGTNTSNQVAVLYQDV PGTNTSNQVAVLYQGV 450 198
HLA-DQA1*01:03/DQB1*06:02 TSNQVAVLYQDVNCT TSNQVAVLYQGVNCT 530 235
HLA-DQA1*01:03/DQB1*06:02 NTSNQVAVLYQDVNCT NTSNQVAVLYQGVNCT 597 268
HLA-DQA1*01:03/DQB1*06:02 TSNQVAVLYQDVNCTE TSNQVAVLYQGVNCTE 838 380
HLA-DQA1*01:03/DQB1*06:02 PGTNTSNQVAVLYQDVN PGTNTSNQVAVLYQGVN 447 206
HLA-DQA1*01:03/DQB1*06:02 PGTNTSNQVAVLYQD PGTNTSNQVAVLYQG 471 218
HLA-DQA1*01:03/DQB1*06:02 TNTSNQVAVLYQDVNC TNTSNQVAVLYQGVNC 485 231
HLA-DQA1*01:03/DQB1*06:02 TSNQVAVLYQDVNCTEV TSNQVAVLYQGVNCTEV 936 460
HLA-DQA1*01:03/DQB1*06:02 TPGTNTSNQVAVLYQDV TPGTNTSNQVAVLYQGV 493 243

N protein

T205I

Reference  SQASSRSSSRSRNSSRNSTPGSSRGTSPARMAGNGGDAALALLLLDRLNQL
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    SQASSRSSSRSRNSSRNSTPGSSRGISPARMAGNGGDAALALLLLDRLNQL

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DQA1*01:03/DQB1*06:02 RNSTPGSSRGTSPARMAGNG RNSTPGSSRGISPARMAGNG 974 353
HLA-DQA1*01:03/DQB1*06:02 STPGSSRGTSPARMAGNGG STPGSSRGISPARMAGNGG 1343 490
HLA-DQA1*01:03/DQB1*06:02 NSTPGSSRGTSPARMAGNGG NSTPGSSRGISPARMAGNGG 948 349
HLA-DQA1*01:03/DQB1*06:02 GSSRGTSPARMAGNGGDAAL GSSRGISPARMAGNGGDAAL 954 354
HLA-DQA1*01:03/DQB1*06:02 SSRGTSPARMAGNGGDA SSRGISPARMAGNGGDA 1158 430
HLA-DQA1*01:03/DQB1*06:02 PGSSRGTSPARMAGNGGDA PGSSRGISPARMAGNGGDA 1317 493
HLA-DQA1*01:03/DQB1*06:02 TPGSSRGTSPARMAGNGGD TPGSSRGISPARMAGNGGD 1287 484
HLA-DQA1*01:03/DQB1*06:02 STPGSSRGTSPARMAGNGGD STPGSSRGISPARMAGNGGD 914 345
HLA-DQA1*01:03/DQB1*06:02 TPGSSRGTSPARMAGNGGDA TPGSSRGISPARMAGNGGDA 921 350
HLA-DQA1*01:03/DQB1*06:02 PGSSRGTSPARMAGNGGDAA PGSSRGISPARMAGNGGDAA 931 355
HLA-DQA1*01:03/DQB1*06:02 SSRGTSPARMAGNGGDAALA SSRGISPARMAGNGGDAALA 1041 401
HLA-DQA1*01:03/DQB1*06:02 TPGSSRGTSPARMAGNG TPGSSRGISPARMAGNG 1023 400
HLA-DQA1*01:03/DQB1*06:02 SRNSTPGSSRGTSPARMAGN SRNSTPGSSRGISPARMAGN 1103 432
HLA-DQA1*01:03/DQB1*06:02 SSRGTSPARMAGNGGD SSRGISPARMAGNGGD 967 379
HLA-DQA1*01:03/DQB1*06:02 SSRGTSPARMAGNGG SSRGISPARMAGNGG 803 315
HLA-DQA1*01:03/DQB1*06:02 GSSRGTSPARMAGNGGD GSSRGISPARMAGNGGD 1005 397
HLA-DQA1*01:03/DQB1*06:02 PGSSRGTSPARMAGNGG PGSSRGISPARMAGNGG 1002 399
HLA-DQA1*01:03/DQB1*06:02 SRGTSPARMAGNGGD SRGISPARMAGNGGD 1215 485
HLA-DQA1*01:03/DQB1*06:02 GSSRGTSPARMAGNG GSSRGISPARMAGNG 705 285
HLA-DQA1*01:03/DQB1*06:02 STPGSSRGTSPARMAGN STPGSSRGISPARMAGN 1136 468
HLA-DQA1*01:03/DQB1*06:02 GSSRGTSPARMAGNGG GSSRGISPARMAGNGG 870 362
HLA-DQA1*01:03/DQB1*06:02 PGSSRGTSPARMAGNG PGSSRGISPARMAGNG 822 359
HLA-DQA1*01:03/DQB1*06:02 PGSSRGTSPARMAGN PGSSRGISPARMAGN 749 330
HLA-DQA1*01:03/DQB1*06:02 TPGSSRGTSPARMAGN TPGSSRGISPARMAGN 913 415

NS8 protein

T11K

Reference  MKFLVFLGIITTVAAFHQECSLQSCTQHQPYVVDDP
           |||||||||| |||||||||||||||||||||||||
Mutated    MKFLVFLGIIKTVAAFHQECSLQSCTQHQPYVVDDP

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DQA1*01:03/DQB1*06:02 KFLVFLGIITTVAAF KFLVFLGIIKTVAAF 1057 429
HLA-DQA1*01:03/DQB1*06:02 MKFLVFLGIITTVAA MKFLVFLGIIKTVAA 935 416
HLA-DQA1*01:03/DQB1*06:02 FLVFLGIITTVAAFH FLVFLGIIKTVAAFH 730 353

NSP3 protein

T237A

Reference  GYLKLTDNVYIKNADIVEEAKKVKPTVVVNAANVYLKHGGGVAGALNKATN
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    GYLKLTDNVYIKNADIVEEAKKVKPAVVVNAANVYLKHGGGVAGALNKATN

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DQA1*01:03/DQB1*06:02 DIVEEAKKVKPTVVVNA DIVEEAKKVKPAVVVNA 600 211
HLA-DQA1*01:03/DQB1*06:02 KNADIVEEAKKVKPTVVVNA KNADIVEEAKKVKPAVVVNA 505 178
HLA-DQA1*01:03/DQB1*06:02 NADIVEEAKKVKPTVVVNA NADIVEEAKKVKPAVVVNA 765 275
HLA-DQA1*01:03/DQB1*06:02 ADIVEEAKKVKPTVVVNAA ADIVEEAKKVKPAVVVNAA 359 131
HLA-DQA1*01:03/DQB1*06:02 ADIVEEAKKVKPTVVVNA ADIVEEAKKVKPAVVVNA 1304 482
HLA-DQA1*01:03/DQB1*06:02 IVEEAKKVKPTVVVNA IVEEAKKVKPAVVVNA 473 176
HLA-DQA1*01:03/DQB1*06:02 DIVEEAKKVKPTVVVNAA DIVEEAKKVKPAVVVNAA 635 241
HLA-DQA1*01:03/DQB1*06:02 NADIVEEAKKVKPTVVVNAA NADIVEEAKKVKPAVVVNAA 227 87
HLA-DQA1*01:03/DQB1*06:02 IVEEAKKVKPTVVVNAA IVEEAKKVKPAVVVNAA 274 106
HLA-DQA1*01:03/DQB1*06:02 VEEAKKVKPTVVVNA VEEAKKVKPAVVVNA 391 152
HLA-DQA1*01:03/DQB1*06:02 DIVEEAKKVKPTVVVNAAN DIVEEAKKVKPAVVVNAAN 278 110
HLA-DQA1*01:03/DQB1*06:02 ADIVEEAKKVKPTVVVNAAN ADIVEEAKKVKPAVVVNAAN 174 70
HLA-DQA1*01:03/DQB1*06:02 IVEEAKKVKPTVVVNAANV IVEEAKKVKPAVVVNAANV 195 79
HLA-DQA1*01:03/DQB1*06:02 VEEAKKVKPTVVVNAA VEEAKKVKPAVVVNAA 219 90
HLA-DQA1*01:03/DQB1*06:02 IVEEAKKVKPTVVVNAAN IVEEAKKVKPAVVVNAAN 503 207
HLA-DQA1*01:03/DQB1*06:02 VEEAKKVKPTVVVNAANV VEEAKKVKPAVVVNAANV 364 150
HLA-DQA1*01:03/DQB1*06:02 VEEAKKVKPTVVVNAAN VEEAKKVKPAVVVNAAN 220 92
HLA-DQA1*01:03/DQB1*06:02 DIVEEAKKVKPTVVVNAANV DIVEEAKKVKPAVVVNAANV 124 52
HLA-DQA1*01:03/DQB1*06:02 EAKKVKPTVVVNAANVYL EAKKVKPAVVVNAANVYL 349 147
HLA-DQA1*01:03/DQB1*06:02 EEAKKVKPTVVVNAANVY EEAKKVKPAVVVNAANVY 344 145
HLA-DQA1*01:03/DQB1*06:02 EAKKVKPTVVVNAANV EAKKVKPAVVVNAANV 135 57
HLA-DQA1*01:03/DQB1*06:02 VEEAKKVKPTVVVNAANVY VEEAKKVKPAVVVNAANVY 180 76
HLA-DQA1*01:03/DQB1*06:02 EEAKKVKPTVVVNAA EEAKKVKPAVVVNAA 196 84
HLA-DQA1*01:03/DQB1*06:02 EEAKKVKPTVVVNAANV EEAKKVKPAVVVNAANV 158 68
HLA-DQA1*01:03/DQB1*06:02 EEAKKVKPTVVVNAAN EEAKKVKPAVVVNAAN 181 78
HLA-DQA1*01:03/DQB1*06:02 IVEEAKKVKPTVVVNAANVY IVEEAKKVKPAVVVNAANVY 116 50
HLA-DQA1*01:03/DQB1*06:02 AKKVKPTVVVNAANV AKKVKPAVVVNAANV 129 56
HLA-DQA1*01:03/DQB1*06:02 VEEAKKVKPTVVVNAANVYL VEEAKKVKPAVVVNAANVYL 115 50
HLA-DQA1*01:03/DQB1*06:02 EEAKKVKPTVVVNAANVYL EEAKKVKPAVVVNAANVYL 177 77
HLA-DQA1*01:03/DQB1*06:02 EAKKVKPTVVVNAAN EAKKVKPAVVVNAAN 172 76
HLA-DQA1*01:03/DQB1*06:02 EAKKVKPTVVVNAANVY EAKKVKPAVVVNAANVY 146 66
HLA-DQA1*01:03/DQB1*06:02 AKKVKPTVVVNAANVY AKKVKPAVVVNAANVY 127 58
HLA-DQA1*01:03/DQB1*06:02 AKKVKPTVVVNAANVYL AKKVKPAVVVNAANVYL 147 68
HLA-DQA1*01:03/DQB1*06:02 KKVKPTVVVNAANVY KKVKPAVVVNAANVY 139 65
HLA-DQA1*01:03/DQB1*06:02 KKVKPTVVVNAANVYL KKVKPAVVVNAANVYL 150 72
HLA-DQA1*01:03/DQB1*06:02 AKKVKPTVVVNAANVYLK AKKVKPAVVVNAANVYLK 299 144
HLA-DQA1*01:03/DQB1*06:02 EEAKKVKPTVVVNAANVYLK EEAKKVKPAVVVNAANVYLK 94 46

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*06:02 VFPPTSFGPLVRKIFV VFPLTSFGPLVRKIFV 1059 482
HLA-DQA1*01:03/DQB1*06:02 VFPPTSFGPLVRKIF VFPLTSFGPLVRKIF 969 456
HLA-DQA1*01:03/DQB1*06:02 FSTVFPPTSFGPLVRKIFVD FSTVFPLTSFGPLVRKIFVD 973 472
HLA-DQA1*01:03/DQB1*06:02 LHCANFNVLFSTVFPPTSFG LHCANFNVLFSTVFPLTSFG 446 902