Summary

This strain contains 25 protein-level mutations:

  • 7 mutations in Spike protein: EFR 156-158 deletion, E484K, S494P, D614G, E780A, D839V, T1027I
  • 3 mutations in N protein: A12S, 203-204 RG->KR, G212C
  • 1 mutation in M protein: I82T
  • 2 mutations in NS3 protein: S171L, V201F
  • 1 mutation in NS9b protein: M8I
  • 1 mutation in NS9c protein: G50N
  • 1 mutation in NSP2 protein: N269D
  • 3 mutations in NSP3 protein: M84V, R1297I, S1375Y
  • 1 mutation in NSP6 protein: V84F
  • 1 mutation in NSP10 protein: T111I
  • 2 mutations in NSP12 protein: S229N, P323L
  • 2 mutations in NSP13 protein: P77L, L455M

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-A*02:11 and peptides affected by the mutations

Weaker binding was found for 24 epitopes, while stronger binding was found for 63 entries. There are 1072 tight binders for the HLA-A*02:11 in the reference immunopeptidome (IC50 affinity ≤ 50 nM); 7 of them became non-tight binders (0.7%) and 14 novel tight binders appeared (1.3%). To avoid possible divisions by zero, we used + 1 regularization term in denominators when calculating percentages.

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HLA-A*02:11

Spike protein

EFR 156-158 deletion

Reference  CEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQ
           |||||||||||||||||||||||||   |||||||||||||||||||||||||
Mutated    CEFQFCNDPFLGVYYHKNNKSWMES‑‑‑VYSSANNCTFEYVSQPFLMDLEGKQ

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:11 WMESEFRV WMESV 156 -
HLA-A*02:11 KSWMESEFRV KSWMESV 212 -
HLA-A*02:11 SEFRVYSSANNCTFEYV SVYSSANNCTFEYV - 249
HLA-A*02:11 SWMESEFRV SWMESV 262 -
HLA-A*02:11 RVYSSANNCTFEYV - 267 -
HLA-A*02:11 WMESEFRVYSSA WMESVYSSA 1678 151

E484K

Reference  SNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYR
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    SNLKPFERDISTEIYQAGSTPCNGVKGFNCYFPLQPYGFQPTNGVGYQPYR

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:11 EGFNCYFPL KGFNCYFPL 2508 259

D614G

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

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:11 DVNCTEVPV GVNCTEVPV 2140 72
HLA-A*02:11 QVAVLYQDV QVAVLYQGV 2169 268
HLA-A*02:11 VLYQDVNCT VLYQGVNCT 224 74
HLA-A*02:11 YQDVNCTEV YQGVNCTEV 31 93
HLA-A*02:11 VLYQDVNCTEVP VLYQGVNCTEVP 1000 402
HLA-A*02:11 AVLYQDVNCTEV AVLYQGVNCTEV 500 238

E780A

Reference  QYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQI
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    QYGSFCTQLNRALTGIAVEQDKNTQAVFAQVKQIYKTPPIKDFGGFNFSQI

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:11 EVFAQVKQI AVFAQVKQI 6830 291
HLA-A*02:11 KNTQEVFAQV KNTQAVFAQV 162 447
HLA-A*02:11 NTQEVFAQV NTQAVFAQV 25 60

D839V

Reference  KRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPL
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    KRSFIEDLLFNKVTLADAGFIKQYGVCLGDIAARDLICAQKFNGLTVLPPL

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:11 TLADAGFIKQYGD TLADAGFIKQYGV 26741 36
HLA-A*02:11 KQYGDCLGDI KQYGVCLGDI 594 248

T1027I

Reference  QSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSF
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    QSLQTYVTQQLIRAAEIRASANLAAIKMSECVLGQSKRVDFCGKGYHLMSF

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:11 NLAATKMSECV NLAAIKMSECV 647 232

M protein

I82T

Reference  LWPVTLACFVLAAVYRINWITGGIAIAMACLVGLMWLSYFIASFRLFARTR
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    LWPVTLACFVLAAVYRINWITGGIATAMACLVGLMWLSYFIASFRLFARTR

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:11 WITGGIAIA WITGGIATA 788 138
HLA-A*02:11 AIAMACLVGL ATAMACLVGL 53 208
HLA-A*02:11 IAIAMACLV IATAMACLV 140 524
HLA-A*02:11 GIAIAMACL GIATAMACL 350 144
HLA-A*02:11 IAMACLVGL TAMACLVGL 70 141

NS3 protein

S171L

Reference  FLCWHTNCYDYCIPYNSVTSSIVITSGDGTTSPISEHDYQIGGYTEKWESG
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    FLCWHTNCYDYCIPYNSVTSSIVITLGDGTTSPISEHDYQIGGYTEKWESG

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:11 TSGDGTTSPI TLGDGTTSPI 10425 92
HLA-A*02:11 VTSSIVITS VTSSIVITL 8785 89
HLA-A*02:11 SVTSSIVITS SVTSSIVITL 12237 410

V201F

Reference  TSPISEHDYQIGGYTEKWESGVKDCVVLHSYFTSDYYQLYSTQLSTDTGVE
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    TSPISEHDYQIGGYTEKWESGVKDCFVLHSYFTSDYYQLYSTQLSTDTGVE

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:11 VVLHSYFTS FVLHSYFTS 3221 231

NS9b protein

M8I

Reference  MDPKISEMHPALRLVDPQIQLAVTRMENAVGRD
           ||||||| |||||||||||||||||||||||||
Mutated    MDPKISEIHPALRLVDPQIQLAVTRMENAVGRD

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:11 SEMHPALRLV SEIHPALRLV 122 1116
HLA-A*02:11 EMHPALRLV EIHPALRLV 249 1492
HLA-A*02:11 MHPALRLVDPQIQL IHPALRLVDPQIQL 486 979
HLA-A*02:11 KISEMHPAL KISEIHPAL 14 7

NS9c protein

G50N

Reference  AAVKPLLVPHHVVATVQEIQLQAAVGELLLLEWLAMAVMLLLLCCCLTD
           ||||||||||||||||||||||||| |||||||||||||||||||||||
Mutated    AAVKPLLVPHHVVATVQEIQLQAAVNELLLLEWLAMAVMLLLLCCCLTD

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:11 QLQAAVGEL QLQAAVNEL 120 27
HLA-A*02:11 IQLQAAVGEL IQLQAAVNEL 338 81
HLA-A*02:11 LQAAVGELL LQAAVNELL 386 154
HLA-A*02:11 QLQAAVGELL QLQAAVNELL 303 131
HLA-A*02:11 GELLLLEWLAMA NELLLLEWLAMA 29 61

NSP2 protein

N269D

Reference  VPRASANIGCNHTGVVGEGSEGLNDNLLEILQKEKVNINIVGDFKLNEEIA
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    VPRASANIGCNHTGVVGEGSEGLNDDLLEILQKEKVNINIVGDFKLNEEIA

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:11 NLLEILQKEKV DLLEILQKEKV 36 2285
HLA-A*02:11 NLLEILQKEKVNI DLLEILQKEKVNI 117 5028

NSP3 protein

M84V

Reference  DAVIKTLQPVSELLTPLGIDLDEWSMATYYLFDESGEFKLASHMYCSFYPP
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    DAVIKTLQPVSELLTPLGIDLDEWSVATYYLFDESGEFKLASHMYCSFYPP

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:11 LLTPLGIDLDEWSM LLTPLGIDLDEWSV 5009 138
HLA-A*02:11 GIDLDEWSM GIDLDEWSV 2256 71
HLA-A*02:11 LGIDLDEWSM LGIDLDEWSV 8171 489

R1297I

Reference  VGHTDLMAAYVDNSSLTIKKPNELSRVLGLKTLATHGLAAVNSVPWDTIAN
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    VGHTDLMAAYVDNSSLTIKKPNELSIVLGLKTLATHGLAAVNSVPWDTIAN

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:11 SLTIKKPNELSRVL SLTIKKPNELSIVL 5804 464

S1375Y

Reference  YMPYFFTLLLQLCTFTRSTNSRIKASMPTTIAKNTVKSVGKFCLEASFNYL
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    YMPYFFTLLLQLCTFTRSTNSRIKAYMPTTIAKNTVKSVGKFCLEASFNYL

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:11 SMPTTIAKNTV YMPTTIAKNTV 140 25
HLA-A*02:11 SMPTTIAKNTVKSV YMPTTIAKNTVKSV 444 88

NSP6 protein

V84F

Reference  FVKHKHAFLCLFLLPSLATVAYFNMVYMPASWVMRIMTWLDMVDTSLSGFK
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    FVKHKHAFLCLFLLPSLATVAYFNMFYMPASWVMRIMTWLDMVDTSLSGFK

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:11 ATVAYFNMV ATVAYFNMF 27 8909
HLA-A*02:11 SLATVAYFNMV SLATVAYFNMF 11 2388
HLA-A*02:11 PSLATVAYFNMV PSLATVAYFNMF 169 14714
HLA-A*02:11 LLPSLATVAYFNMV LLPSLATVAYFNMF 494 16064
HLA-A*02:11 SLATVAYFNMVY SLATVAYFNMFY 352 6801
HLA-A*02:11 MVYMPASWV MFYMPASWV 18 331
HLA-A*02:11 MVYMPASWVM MFYMPASWVM 279 2115
HLA-A*02:11 NMVYMPASWV NMFYMPASWV 72 15
HLA-A*02:11 NMVYMPASWVMRI NMFYMPASWVMRI 471 102
HLA-A*02:11 VAYFNMVYM VAYFNMFYM 515 117
HLA-A*02:11 TVAYFNMVYM TVAYFNMFYM 638 216
HLA-A*02:11 MVYMPASWVMRI MFYMPASWVMRI 176 411
HLA-A*02:11 SLATVAYFNMVYM SLATVAYFNMFYM 152 69

NSP10 protein

T111I

Reference  PKGFCDLKGKYVQIPTTCANDPVGFTLKNTVCTVCGMWKGYGCSCDQLREP
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    PKGFCDLKGKYVQIPTTCANDPVGFILKNTVCTVCGMWKGYGCSCDQLREP

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:11 FTLKNTVCT FILKNTVCT 1421 327
HLA-A*02:11 TLKNTVCTV ILKNTVCTV 14 7

NSP12 protein

P323L

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

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:11 FPPTSFGPLV FPLTSFGPLV 3405 9
HLA-A*02:11 LFSTVFPP LFSTVFPL 6706 35
HLA-A*02:11 ANFNVLFSTVFPP ANFNVLFSTVFPL 1827 12
HLA-A*02:11 NFNVLFSTVFPP NFNVLFSTVFPL 1779 13
HLA-A*02:11 NVLFSTVFPP NVLFSTVFPL 739 6
HLA-A*02:11 FNVLFSTVFPP FNVLFSTVFPL 413 4
HLA-A*02:11 FNVLFSTVFPPT FNVLFSTVFPLT 2618 27
HLA-A*02:11 VLFSTVFPP VLFSTVFPL 78 1
HLA-A*02:11 FNVLFSTVFPPTS FNVLFSTVFPLTS 9448 142
HLA-A*02:11 CANFNVLFSTVFPP CANFNVLFSTVFPL 6143 96
HLA-A*02:11 PPTSFGPLV PLTSFGPLV 28329 483
HLA-A*02:11 FSTVFPPTSFGPLV FSTVFPLTSFGPLV 6695 180
HLA-A*02:11 ANFNVLFSTVFPPT ANFNVLFSTVFPLT 14639 409
HLA-A*02:11 VFPPTSFGPLV VFPLTSFGPLV 4242 199
HLA-A*02:11 NFNVLFSTVFPPT NFNVLFSTVFPLT 9111 472
HLA-A*02:11 STVFPPTSFGPLV STVFPLTSFGPLV 2427 285
HLA-A*02:11 NVLFSTVFPPT NVLFSTVFPLT 1183 139
HLA-A*02:11 VLFSTVFPPTSF VLFSTVFPLTSF 1019 195
HLA-A*02:11 VLFSTVFPPTS VLFSTVFPLTS 309 74
HLA-A*02:11 VLFSTVFPPT VLFSTVFPLT 25 11

NSP13 protein

P77L

Reference  APGCDVTDVTQLYLGGMSYYCKSHKPPISFPLCANGQVFGLYKNTCVGSDN
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    APGCDVTDVTQLYLGGMSYYCKSHKLPISFPLCANGQVFGLYKNTCVGSDN

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:11 KPPISFPL KLPISFPL 18334 25
HLA-A*02:11 YLGGMSYYCKSHKP YLGGMSYYCKSHKL 7927 24
HLA-A*02:11 KPPISFPLCA KLPISFPLCA 20510 68
HLA-A*02:11 KPPISFPLC KLPISFPLC 17315 110
HLA-A*02:11 GMSYYCKSHKP GMSYYCKSHKL 18709 374
HLA-A*02:11 KPPISFPLCANGQV KLPISFPLCANGQV 22321 498

L455M

Reference  KTIGPDMFLGTCRRCPAEIVDTVSALVYDNKLKAHKDKSAQCFKMFYKGVI
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    KTIGPDMFLGTCRRCPAEIVDTVSAMVYDNKLKAHKDKSAQCFKMFYKGVI

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:11 LVYDNKLKA MVYDNKLKA 882 287