Summary

This strain contains 24 protein-level mutations:

  • 10 mutations in Spike protein: T19R, K77T, G142D, EF 156-157 deletion, R158G, L452R, T478K, D614G, P681R, D950N
  • 3 mutations in N protein: D63G, R203M, D377Y
  • 1 mutation in M protein: I82T
  • 1 mutation in NS3 protein: S26L
  • 2 mutations in NS7a protein: V82A, T120I
  • 1 mutation in NS9b protein: T60A
  • 1 mutation in NS9c protein: G50W
  • 1 mutation in NSP2 protein: P129L
  • 1 mutation in NSP3 protein: P822L
  • 2 mutations in NSP4 protein: D217N, F375S
  • 1 mutation in NSP12 protein: P323L

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-DPA1*02:02/DPB1*05:01 and peptides affected by the mutations

Weaker binding was found for 30 epitopes, while stronger binding was found for 57 entries. There are 4 tight binders for the HLA-DPA1*02:02/DPB1*05:01 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-DPA1*02:02/DPB1*05:01

Spike protein

G142D

Reference  LLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCT
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Mutated    LLIVNNATNVVIKVCEFQFCNDPFLDVYYHKNNKSWMES‑‑GVYSSANNCT

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DPA1*02:02/DPB1*05:01 DPFLGVYYHKNNKSWMESEF DPFLDVYYHKNNKSWMES 475 2807
HLA-DPA1*02:02/DPB1*05:01 NDPFLGVYYHKNNKSWMESE NDPFLDVYYHKNNKSWMES 428 1418

EF 156-157 deletion

Reference  CEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGK
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Mutated    CEFQFCNDPFLDVYYHKNNKSWMES‑‑GVYSSANNCTFEYVSQPFLMDLEGK

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DPA1*02:02/DPB1*05:01 NKSWMESEFRVYSSANNCTF NKSWMESGVYSSANNCTF 327 6848
HLA-DPA1*02:02/DPB1*05:01 KSWMESEFRVYSSANNCTFE KSWMESGVYSSANNCTFE 379 7838
HLA-DPA1*02:02/DPB1*05:01 NNKSWMESEFRVYSSANNCT NNKSWMESGVYSSANNCT 338 6636
HLA-DPA1*02:02/DPB1*05:01 KNNKSWMESEFRVYSSANNC KNNKSWMESGVYSSANNC 318 6024
HLA-DPA1*02:02/DPB1*05:01 HKNNKSWMESEFRVYSSANN HKNNKSWMESGVYSSANN 341 5750
HLA-DPA1*02:02/DPB1*05:01 YHKNNKSWMESEFRVYSSAN YHKNNKSWMESGVYSSAN 428 5703
HLA-DPA1*02:02/DPB1*05:01 YYHKNNKSWMESEFRVYSSA YYHKNNKSWMESGVYSSA 430 5648
HLA-DPA1*02:02/DPB1*05:01 VYYHKNNKSWMESEFRVYSS VYYHKNNKSWMESGVYSS 493 5666
HLA-DPA1*02:02/DPB1*05:01 DPFLGVYYHKNNKSWMESEF DPFLDVYYHKNNKSWMES 475 2807
HLA-DPA1*02:02/DPB1*05:01 NDPFLGVYYHKNNKSWMESE NDPFLDVYYHKNNKSWMES 428 1418

R158G

Reference  FQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQ
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Mutated    FQFCNDPFLDVYYHKNNKSWMES‑‑GVYSSANNCTFEYVSQPFLMDLEGKQ

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DPA1*02:02/DPB1*05:01 NKSWMESEFRVYSSANNCTF NKSWMESGVYSSANNCTF 327 6848
HLA-DPA1*02:02/DPB1*05:01 KSWMESEFRVYSSANNCTFE KSWMESGVYSSANNCTFE 379 7838
HLA-DPA1*02:02/DPB1*05:01 NNKSWMESEFRVYSSANNCT NNKSWMESGVYSSANNCT 338 6636
HLA-DPA1*02:02/DPB1*05:01 KNNKSWMESEFRVYSSANNC KNNKSWMESGVYSSANNC 318 6024
HLA-DPA1*02:02/DPB1*05:01 HKNNKSWMESEFRVYSSANN HKNNKSWMESGVYSSANN 341 5750
HLA-DPA1*02:02/DPB1*05:01 YHKNNKSWMESEFRVYSSAN YHKNNKSWMESGVYSSAN 428 5703
HLA-DPA1*02:02/DPB1*05:01 YYHKNNKSWMESEFRVYSSA YYHKNNKSWMESGVYSSA 430 5648
HLA-DPA1*02:02/DPB1*05:01 VYYHKNNKSWMESEFRVYSS VYYHKNNKSWMESGVYSS 493 5666

L452R

Reference  DDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGS
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Mutated    DDFTGCVIAWNSNNLDSKVGGNYNYRYRLFRKSNLKPFERDISTEIYQAGS

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DPA1*02:02/DPB1*05:01 KVGGNYNYLYRLFRK KVGGNYNYRYRLFRK 351 1116
HLA-DPA1*02:02/DPB1*05:01 DSKVGGNYNYLYRLFRK DSKVGGNYNYRYRLFRK 425 1331
HLA-DPA1*02:02/DPB1*05:01 SKVGGNYNYLYRLFRK SKVGGNYNYRYRLFRK 446 1378
HLA-DPA1*02:02/DPB1*05:01 NNLDSKVGGNYNYLYRLFRK NNLDSKVGGNYNYRYRLFRK 347 927
HLA-DPA1*02:02/DPB1*05:01 LDSKVGGNYNYLYRLFRKS LDSKVGGNYNYRYRLFRKS 294 622
HLA-DPA1*02:02/DPB1*05:01 KVGGNYNYLYRLFRKS KVGGNYNYRYRLFRKS 240 492
HLA-DPA1*02:02/DPB1*05:01 SKVGGNYNYLYRLFRKS SKVGGNYNYRYRLFRKS 224 454
HLA-DPA1*02:02/DPB1*05:01 DSKVGGNYNYLYRLFRKSN DSKVGGNYNYRYRLFRKSN 265 537
HLA-DPA1*02:02/DPB1*05:01 VGGNYNYLYRLFRKS VGGNYNYRYRLFRKS 198 399
HLA-DPA1*02:02/DPB1*05:01 GGNYNYLYRLFRKSN GGNYNYRYRLFRKSN 184 368

N protein

D377Y

Reference  LLNKHIDAYKTFPPTEPKKDKKKKADETQALPQRQKKQQTVTLLPAADLDD
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Mutated    LLNKHIDAYKTFPPTEPKKDKKKKAYETQALPQRQKKQQTVTLLPAADLDD

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DPA1*02:02/DPB1*05:01 KKDKKKKADETQALPQRQKK KKDKKKKAYETQALPQRQKK 3065 439
HLA-DPA1*02:02/DPB1*05:01 KDKKKKADETQALPQRQKKQ KDKKKKAYETQALPQRQKKQ 2962 438
HLA-DPA1*02:02/DPB1*05:01 DKKKKADETQALPQRQKKQQ DKKKKAYETQALPQRQKKQQ 3012 449
HLA-DPA1*02:02/DPB1*05:01 PKKDKKKKADETQALPQRQK PKKDKKKKAYETQALPQRQK 3303 499
HLA-DPA1*02:02/DPB1*05:01 KKKKADETQALPQRQKKQQT KKKKAYETQALPQRQKKQQT 2863 459

NSP3 protein

P822L

Reference  GKTFYVLPNDDTLRVEAFEYYHTTDPSFLGRYMSALNHTKKWKYPQVNGLT
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Mutated    GKTFYVLPNDDTLRVEAFEYYHTTDLSFLGRYMSALNHTKKWKYPQVNGLT

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DPA1*02:02/DPB1*05:01 EAFEYYHTTDPSFLGRYMSA EAFEYYHTTDLSFLGRYMSA 1436 352
HLA-DPA1*02:02/DPB1*05:01 VEAFEYYHTTDPSFLGRYMS VEAFEYYHTTDLSFLGRYMS 1304 363
HLA-DPA1*02:02/DPB1*05:01 AFEYYHTTDPSFLGRYMSAL AFEYYHTTDLSFLGRYMSAL 1111 343
HLA-DPA1*02:02/DPB1*05:01 RVEAFEYYHTTDPSFLGRYM RVEAFEYYHTTDLSFLGRYM 1012 350
HLA-DPA1*02:02/DPB1*05:01 FEYYHTTDPSFLGRYMSALN FEYYHTTDLSFLGRYMSALN 877 348
HLA-DPA1*02:02/DPB1*05:01 LRVEAFEYYHTTDPSFLGRY LRVEAFEYYHTTDLSFLGRY 616 304
HLA-DPA1*02:02/DPB1*05:01 EYYHTTDPSFLGRYMSALNH EYYHTTDLSFLGRYMSALNH 727 360

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-DPA1*02:02/DPB1*05:01 FSTVFPPTSFGPLVRK FSTVFPLTSFGPLVRK 1892 258
HLA-DPA1*02:02/DPB1*05:01 STVFPPTSFGPLVRK STVFPLTSFGPLVRK 1460 206
HLA-DPA1*02:02/DPB1*05:01 FSTVFPPTSFGPLVRKI FSTVFPLTSFGPLVRKI 1268 183
HLA-DPA1*02:02/DPB1*05:01 STVFPPTSFGPLVRKI STVFPLTSFGPLVRKI 1545 223
HLA-DPA1*02:02/DPB1*05:01 TVFPPTSFGPLVRKI TVFPLTSFGPLVRKI 1200 179
HLA-DPA1*02:02/DPB1*05:01 FSTVFPPTSFGPLVR FSTVFPLTSFGPLVR 2073 327
HLA-DPA1*02:02/DPB1*05:01 FSTVFPPTSFGPLVRKIF FSTVFPLTSFGPLVRKIF 1809 299
HLA-DPA1*02:02/DPB1*05:01 LFSTVFPPTSFGPLVRKI LFSTVFPLTSFGPLVRKI 2178 366
HLA-DPA1*02:02/DPB1*05:01 LFSTVFPPTSFGPLVRK LFSTVFPLTSFGPLVRK 1133 195
HLA-DPA1*02:02/DPB1*05:01 TVFPPTSFGPLVRKIFVD TVFPLTSFGPLVRKIFVD 1849 334
HLA-DPA1*02:02/DPB1*05:01 STVFPPTSFGPLVRKIF STVFPLTSFGPLVRKIF 844 153
HLA-DPA1*02:02/DPB1*05:01 STVFPPTSFGPLVRKIFV STVFPLTSFGPLVRKIFV 1627 298
HLA-DPA1*02:02/DPB1*05:01 VFPPTSFGPLVRKIFVDG VFPLTSFGPLVRKIFVDG 2065 380
HLA-DPA1*02:02/DPB1*05:01 TVFPPTSFGPLVRKIF TVFPLTSFGPLVRKIF 970 183
HLA-DPA1*02:02/DPB1*05:01 VFPPTSFGPLVRKIF VFPLTSFGPLVRKIF 832 159
HLA-DPA1*02:02/DPB1*05:01 VFPPTSFGPLVRKIFVD VFPLTSFGPLVRKIFVD 858 175
HLA-DPA1*02:02/DPB1*05:01 TVFPPTSFGPLVRKIFV TVFPLTSFGPLVRKIFV 746 155
HLA-DPA1*02:02/DPB1*05:01 VFPPTSFGPLVRKIFV VFPLTSFGPLVRKIFV 891 192
HLA-DPA1*02:02/DPB1*05:01 FPPTSFGPLVRKIFVD FPLTSFGPLVRKIFVD 1222 271
HLA-DPA1*02:02/DPB1*05:01 FPPTSFGPLVRKIFVDG FPLTSFGPLVRKIFVDG 1083 242
HLA-DPA1*02:02/DPB1*05:01 FPPTSFGPLVRKIFV FPLTSFGPLVRKIFV 909 204
HLA-DPA1*02:02/DPB1*05:01 LFSTVFPPTSFGPLVR LFSTVFPLTSFGPLVR 1614 375
HLA-DPA1*02:02/DPB1*05:01 STVFPPTSFGPLVRKIFVD STVFPLTSFGPLVRKIFVD 975 228
HLA-DPA1*02:02/DPB1*05:01 FSTVFPPTSFGPLVRKIFV FSTVFPLTSFGPLVRKIFV 884 210
HLA-DPA1*02:02/DPB1*05:01 TVFPPTSFGPLVRKIFVDG TVFPLTSFGPLVRKIFVDG 1041 252
HLA-DPA1*02:02/DPB1*05:01 VLFSTVFPPTSFGPLVRK VLFSTVFPLTSFGPLVRK 1562 386
HLA-DPA1*02:02/DPB1*05:01 FSTVFPPTSFGPLVRKIFVD FSTVFPLTSFGPLVRKIFVD 526 130
HLA-DPA1*02:02/DPB1*05:01 STVFPPTSFGPLVRKIFVDG STVFPLTSFGPLVRKIFVDG 561 139
HLA-DPA1*02:02/DPB1*05:01 LFSTVFPPTSFGPLVRKIF LFSTVFPLTSFGPLVRKIF 846 210
HLA-DPA1*02:02/DPB1*05:01 PPTSFGPLVRKIFVD PLTSFGPLVRKIFVD 1309 336
HLA-DPA1*02:02/DPB1*05:01 TVFPPTSFGPLVRKIFVDGV TVFPLTSFGPLVRKIFVDGV 532 143
HLA-DPA1*02:02/DPB1*05:01 VFPPTSFGPLVRKIFVDGV VFPLTSFGPLVRKIFVDGV 1012 273
HLA-DPA1*02:02/DPB1*05:01 VLFSTVFPPTSFGPLVRKI VLFSTVFPLTSFGPLVRKI 800 227
HLA-DPA1*02:02/DPB1*05:01 PPTSFGPLVRKIFVDG PLTSFGPLVRKIFVDG 1562 446
HLA-DPA1*02:02/DPB1*05:01 LFSTVFPPTSFGPLVRKIFV LFSTVFPLTSFGPLVRKIFV 443 128
HLA-DPA1*02:02/DPB1*05:01 VFPPTSFGPLVRKIFVDGVP VFPLTSFGPLVRKIFVDGVP 535 161
HLA-DPA1*02:02/DPB1*05:01 PPTSFGPLVRKIFVDGV PLTSFGPLVRKIFVDGV 1157 366
HLA-DPA1*02:02/DPB1*05:01 VLFSTVFPPTSFGPLVRKIF VLFSTVFPLTSFGPLVRKIF 405 129
HLA-DPA1*02:02/DPB1*05:01 FPPTSFGPLVRKIFVDGVP FPLTSFGPLVRKIFVDGVP 1128 363
HLA-DPA1*02:02/DPB1*05:01 VLFSTVFPPTSFGPLVR VLFSTVFPLTSFGPLVR 763 253
HLA-DPA1*02:02/DPB1*05:01 NVLFSTVFPPTSFGPLVRKI NVLFSTVFPLTSFGPLVRKI 403 134
HLA-DPA1*02:02/DPB1*05:01 NVLFSTVFPPTSFGPLVRK NVLFSTVFPLTSFGPLVRK 680 238
HLA-DPA1*02:02/DPB1*05:01 FPPTSFGPLVRKIFVDGVPF FPLTSFGPLVRKIFVDGVPF 514 195
HLA-DPA1*02:02/DPB1*05:01 FNVLFSTVFPPTSFGPLVRK FNVLFSTVFPLTSFGPLVRK 337 147
HLA-DPA1*02:02/DPB1*05:01 PPTSFGPLVRKIFVDGVPF PLTSFGPLVRKIFVDGVPF 1018 494