Summary

This strain contains 49 protein-level mutations:

  • 26 mutations in Spike protein: T19I, G142D, V213G, G339D, S371F, S373P, 375-376 ST->FA, D405N, R408S, K417N, N440K, L452R, 477-478 ST->NK, E484A, F486V, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, N969K
  • 4 mutations in N protein: P13L, R32C, 203-204 RG->KR, S413R
  • 3 mutations in M protein: D3N, Q19E, A63T
  • 1 mutation in E protein: T9I
  • 1 mutation in NS3 protein: T223I
  • 1 mutation in NS9b protein: P10S
  • 1 mutation in NS9c protein: G50N
  • 1 mutation in NSP1 protein: S135R
  • 2 mutations in NSP3 protein: T24I, G489S
  • 3 mutations in NSP4 protein: L264F, T327I, T492I
  • 1 mutation in NSP5 protein: P132H
  • 1 mutation in NSP6 protein: F108L
  • 1 mutation in NSP12 protein: P323L
  • 2 mutations in NSP13 protein: R392C, T481M
  • 1 mutation in NSP15 protein: T112I

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-C*03:02 and peptides affected by the mutations

Weaker binding was found for 17 epitopes, while stronger binding was found for 33 entries. There are 198 tight binders for the HLA-C*03:02 in the reference immunopeptidome (IC50 affinity ≤ 50 nM); 1 of them became non-tight binders (0.5%) and 2 novel tight binders appeared (1.0%). To avoid possible divisions by zero, we used + 1 regularization term in denominators when calculating percentages.

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HLA-C*03:02

Spike protein

V213G

Reference  NLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRF
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    NLREFVFKNIDGYFKIYSKHTPINLGRDLPQGFSALEPLVDLPIGINITRF

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*03:02 LVRDLPQGF LGRDLPQGF 259 1765

S371F

Reference  RFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVY
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    RFASVYAWNRKRISNCVADYSVLYNFAPFFAFKCYGVSPTKLNDLCFTNVY

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*03:02 VLYNSASFS VLYNFAPFF 13004 222
HLA-C*03:02 VADYSVLYNS VADYSVLYNF 20606 367
HLA-C*03:02 SVLYNSASFS SVLYNFAPFF 8888 443
HLA-C*03:02 YSVLYNSASFS YSVLYNFAPFF 2405 264
HLA-C*03:02 YSVLYNSASFSTF YSVLYNFAPFFAF 113 329
HLA-C*03:02 SASFSTFKCY FAPFFAFKCY 212 97

S373P

Reference  ASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYAD
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    ASVYAWNRKRISNCVADYSVLYNFAPFFAFKCYGVSPTKLNDLCFTNVYAD

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*03:02 VLYNSASFS VLYNFAPFF 13004 222
HLA-C*03:02 ASFSTFKCY APFFAFKCY 64 2656
HLA-C*03:02 SVLYNSASFS SVLYNFAPFF 8888 443
HLA-C*03:02 YSVLYNSASFS YSVLYNFAPFF 2405 264
HLA-C*03:02 YSVLYNSASFSTF YSVLYNFAPFFAF 113 329
HLA-C*03:02 SASFSTFKCY FAPFFAFKCY 212 97

375-376 ST->FA

Reference  VYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFV
           |||||||||||||||||||||||||  |||||||||||||||||||||||||
Mutated    VYAWNRKRISNCVADYSVLYNFAPFFAFKCYGVSPTKLNDLCFTNVYADSFV

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*03:02 VLYNSASFS VLYNFAPFF 13004 222
HLA-C*03:02 ASFSTFKCY APFFAFKCY 64 2656
HLA-C*03:02 SVLYNSASFS SVLYNFAPFF 8888 443
HLA-C*03:02 STFKCYGVS FAFKCYGVS 8370 424
HLA-C*03:02 YSVLYNSASFS YSVLYNFAPFF 2405 264
HLA-C*03:02 YSVLYNSASFSTF YSVLYNFAPFFAF 113 329
HLA-C*03:02 SASFSTFKCY FAPFFAFKCY 212 97

F486V

Reference  LKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVV
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    LKPFERDISTEIYQAGNKPCNGVAGVNCYFPLQSYGFRPTYGVGHQPYRVV

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*03:02 FNCYFPLQSY VNCYFPLQSY 225 1964

Q498R

Reference  YQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPAT
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    YQAGNKPCNGVAGVNCYFPLQSYGFRPTYGVGHQPYRVVVLSFELLHAPAT

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*03:02 QSYGFQPTN QSYGFRPTY 12903 18
HLA-C*03:02 FPLQSYGFQPTN FPLQSYGFRPTY 23840 111
HLA-C*03:02 LQSYGFQPTN LQSYGFRPTY 23421 125
HLA-C*03:02 YFPLQSYGFQPTN YFPLQSYGFRPTY 27639 176

N501Y

Reference  GSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCG
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    GNKPCNGVAGVNCYFPLQSYGFRPTYGVGHQPYRVVVLSFELLHAPATVCG

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*03:02 QSYGFQPTN QSYGFRPTY 12903 18
HLA-C*03:02 FPLQSYGFQPTN FPLQSYGFRPTY 23840 111
HLA-C*03:02 LQSYGFQPTN LQSYGFRPTY 23421 125
HLA-C*03:02 YFPLQSYGFQPTN YFPLQSYGFRPTY 27639 176
HLA-C*03:02 NGVGYQPY YGVGHQPY 10463 322

Y505H

Reference  CNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKS
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    CNGVAGVNCYFPLQSYGFRPTYGVGHQPYRVVVLSFELLHAPATVCGPKKS

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*03:02 NGVGYQPY YGVGHQPY 10463 322

N764K

Reference  TMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIY
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    TMYICGDSTECSNLLLQYGSFCTQLKRALTGIAVEQDKNTQEVFAQVKQIY

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*03:02 FCTQLNRAL FCTQLKRAL 361 1438

M protein

A63T

Reference  AYANRNRFLYIIKLIFLWLLWPVTLACFVLAAVYRINWITGGIAIAMACLV
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    AYANRNRFLYIIKLIFLWLLWPVTLTCFVLAAVYRINWITGGIAIAMACLV

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*03:02 LACFVLAAVY LTCFVLAAVY 145 935

NS3 protein

T223I

Reference  KDCVVLHSYFTSDYYQLYSTQLSTDTGVEHVTFFIYNKIVDEPEEHVQIHT
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    KDCVVLHSYFTSDYYQLYSTQLSTDIGVEHVTFFIYNKIVDEPEEHVQIHT

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*03:02 YSTQLSTDT YSTQLSTDI 6466 347
HLA-C*03:02 TGVEHVTFF IGVEHVTFF 237 88

NSP1 protein

S135R

Reference  HVGEIPVAYRKVLLRKNGNKGAGGHSYGADLKSFDLGDELGTDPYEDFQEN
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    HVGEIPVAYRKVLLRKNGNKGAGGHRYGADLKSFDLGDELGTDPYEDFQEN

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*03:02 HSYGADLKSF HRYGADLKSF 94 6500

NSP3 protein

T24I

Reference  APTKVTFGDDTVIEVQGYKSVNITFELDERIDKVLNEKCSAYTVELGTE
           ||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    APTKVTFGDDTVIEVQGYKSVNIIFELDERIDKVLNEKCSAYTVELGTE

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*03:02 YKSVNITFEL YKSVNIIFEL 299 784

NSP4 protein

L264F

Reference  GRWVLNNDYYRSLPGVFCGVDAVNLLTNMFTPLIQPIGALDISASIVAGGI
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    GRWVLNNDYYRSLPGVFCGVDAVNLFTNMFTPLIQPIGALDISASIVAGGI

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*03:02 LTNMFTPL FTNMFTPL 829 77
HLA-C*03:02 LTNMFTPLI FTNMFTPLI 716 87
HLA-C*03:02 LLTNMFTPL LFTNMFTPL 307 951

T327I

Reference  MRFRRAFGEYSHVVAFNTLLFLMSFTVLCLTPVYSFLPGVYSVIYLYLTFY
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    MRFRRAFGEYSHVVAFNTLLFLMSFIVLCLTPVYSFLPGVYSVIYLYLTFY

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*03:02 FTVLCLTPV FIVLCLTPV 198 902
HLA-C*03:02 FLMSFTVL FLMSFIVL 352 1285
HLA-C*03:02 FTVLCLTPVY FIVLCLTPVY 50 175
HLA-C*03:02 LMSFTVLCL LMSFIVLCL 467 1520
HLA-C*03:02 TVLCLTPVY IVLCLTPVY 136 54

NSP6 protein

F108L

Reference  MVYMPASWVMRIMTWLDMVDTSLSGFKLKDCVMYASAVVLLILMTARTVYD
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    MVYMPASWVMRIMTWLDMVDTSLSGLKLKDCVMYASAVVLLILMTARTVYD

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*03:02 MVDTSLSGF MVDTSLSGL 211 952

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-C*03:02 VLFSTVFPP VLFSTVFPL 20533 273
HLA-C*03:02 FPPTSFGPL FPLTSFGPL 960 313

NSP13 protein

T481M

Reference  VYDNKLKAHKDKSAQCFKMFYKGVITHDVSSAINRPQIGVVREFLTRNPAW
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    VYDNKLKAHKDKSAQCFKMFYKGVIMHDVSSAINRPQIGVVREFLTRNPAW

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*03:02 KMFYKGVIT KMFYKGVIM 12717 219
HLA-C*03:02 FKMFYKGVIT FKMFYKGVIM 14570 282