Summary

This strain contains 48 protein-level mutations:

  • 29 mutations in Spike protein: A67V, HV 69-70 deletion, T95I, GVY 142-144 deletion, Y145D, N211 deletion, L212I, EPE 212-214 insertion, G339D, S371L, S373P, S375F, 477-478 ST->NK, E484A, Q493R, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, D796Y, N856K, Q954H, N969K, L981F
  • 3 mutations in N protein: P13L, ERS 31-33 deletion, 203-204 RG->KR
  • 3 mutations in M protein: D3G, Q19E, A63T
  • 1 mutation in E protein: T9I
  • 2 mutations in NS9b protein: P10S, ENA 27-29 deletion
  • 1 mutation in NS9c protein: G50N
  • 4 mutations in NSP3 protein: K38R, S1265 deletion, L1266I, A1892T
  • 1 mutation in NSP4 protein: T492I
  • 1 mutation in NSP5 protein: P132H
  • 2 mutations in NSP6 protein: LSG 105-107 deletion, I189V
  • 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-A*02:06 and peptides affected by the mutations

Weaker binding was found for 39 epitopes, while stronger binding was found for 58 entries. There are 363 tight binders for the HLA-A*02:06 in the reference immunopeptidome (IC50 affinity ≤ 50 nM); 6 of them became non-tight binders (1.6%) and 12 novel tight binders appeared (3.3%). To avoid possible divisions by zero, we used + 1 regularization term in denominators when calculating percentages.

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HLA-A*02:06

Spike protein

A67V

Reference  VFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYF
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    VFRSSVLHSTQDLFLPFFSNVTWFHVI‑‑SGTNGTKRFDNPVLPFNDGVYF

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 VTWFHAIHV VTWFHVI 40 -
HLA-A*02:06 NVTWFHAIHV NVTWFHVI 263 10869
HLA-A*02:06 FSNVTWFHAIH FSNVTWFHVI 7820 387
HLA-A*02:06 FSNVTWFHA FSNVTWFHV 182 24
HLA-A*02:06 FFSNVTWFHA FFSNVTWFHV 972 227
HLA-A*02:06 SNVTWFHAI SNVTWFHVI 317 1145
HLA-A*02:06 FLPFFSNVTWFHA FLPFFSNVTWFHV 608 172
HLA-A*02:06 FLPFFSNVTWFHAI FLPFFSNVTWFHVI 457 1475
HLA-A*02:06 FSNVTWFHAI FSNVTWFHVI 123 387

HV 69-70 deletion

Reference  RSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFAST
           |||||||||||||||||||||||||  |||||||||||||||||||||||||
Mutated    RSSVLHSTQDLFLPFFSNVTWFHVI‑‑SGTNGTKRFDNPVLPFNDGVYFASI

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 VTWFHAIHV VTWFHVI 40 -
HLA-A*02:06 NVTWFHAIHV NVTWFHVI 263 10869
HLA-A*02:06 FSNVTWFHAIH FSNVTWFHVI 7820 387

GVY 142-144 deletion

Reference  LLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFE
           |||||||||||||||||||||||||   |||||||||||||||||||||||||
Mutated    LLIVNNATNVVIKVCEFQFCNDPFL‑‑‑DHKNNKSWMESEFRVYSSANNCTFE

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 FQFCNDPFLGV - 7 -
HLA-A*02:06 EFQFCNDPFLGV - 87 -
HLA-A*02:06 FCNDPFLGV FCNDPFL 116 -
HLA-A*02:06 FQFCNDPFLGVY - 135 -
HLA-A*02:06 FQFCNDPFLG - 207 -
HLA-A*02:06 FQFCNDPFLGVYY FQFCNDPFLD 1024 258

Y145D

Reference  VNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEY
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    VNNATNVVIKVCEFQFCNDPFL‑‑‑DHKNNKSWMESEFRVYSSANNCTFEY

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 FQFCNDPFLGVYY FQFCNDPFLD 1024 258

S371L

Reference  RFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVY
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    RFASVYAWNRKRISNCVADYSVLYNLAPFFTFKCYGVSPTKLNDLCFTNVY

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 NSASFSTFKCYGV NLAPFFTFKCYGV 2140 141
HLA-A*02:06 SVLYNSASF SVLYNLAPF 2112 217
HLA-A*02:06 YSVLYNSASF YSVLYNLAPF 2478 463
HLA-A*02:06 VLYNSASFST VLYNLAPFFT 710 312

S373P

Reference  ASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYAD
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    ASVYAWNRKRISNCVADYSVLYNLAPFFTFKCYGVSPTKLNDLCFTNVYAD

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 ASFSTFKCYGV APFFTFKCYGV 231 13051
HLA-A*02:06 NSASFSTFKCYGV NLAPFFTFKCYGV 2140 141
HLA-A*02:06 SVLYNSASF SVLYNLAPF 2112 217
HLA-A*02:06 YSVLYNSASF YSVLYNLAPF 2478 463
HLA-A*02:06 VLYNSASFST VLYNLAPFFT 710 312

S375F

Reference  VYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSF
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    VYAWNRKRISNCVADYSVLYNLAPFFTFKCYGVSPTKLNDLCFTNVYADSF

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 ASFSTFKCYGV APFFTFKCYGV 231 13051
HLA-A*02:06 FSTFKCYGV FFTFKCYGV 61 2768
HLA-A*02:06 NSASFSTFKCYGV NLAPFFTFKCYGV 2140 141
HLA-A*02:06 STFKCYGV FTFKCYGV 2045 328
HLA-A*02:06 VLYNSASFST VLYNLAPFFT 710 312

477-478 ST->NK

Reference  LYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGV
           |||||||||||||||||||||||||  |||||||||||||||||||||||||
Mutated    LYRLFRKSNLKPFERDISTEIYQAGNKPCNGVAGFNCYFPLRSYSFRPTYGV

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 YQAGSTPCNGV YQAGNKPCNGV 39 146

E484A

Reference  SNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYR
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    SNLKPFERDISTEIYQAGNKPCNGVAGFNCYFPLRSYSFRPTYGVGHQPYR

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 EGFNCYFPL AGFNCYFPL 1266 185
HLA-A*02:06 VEGFNCYFPL VAGFNCYFPL 1553 310
HLA-A*02:06 GVEGFNCYFPL GVAGFNCYFPL 400 174

Q493R

Reference  ISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELL
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    ISTEIYQAGNKPCNGVAGFNCYFPLRSYSFRPTYGVGHQPYRVVVLSFELL

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 LQSYGFQPT LRSYSFRPT 339 27414
HLA-A*02:06 LQSYGFQPTNGV LRSYSFRPTYGV 249 2086
HLA-A*02:06 QSYGFQPTNGV RSYSFRPTYGV 1121 320

G496S

Reference  EIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAP
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    EIYQAGNKPCNGVAGFNCYFPLRSYSFRPTYGVGHQPYRVVVLSFELLHAP

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 LQSYGFQPT LRSYSFRPT 339 27414
HLA-A*02:06 YGFQPTNGV YSFRPTYGV 174 10
HLA-A*02:06 SYGFQPTNGV SYSFRPTYGV 3944 455
HLA-A*02:06 LQSYGFQPTNGV LRSYSFRPTYGV 249 2086
HLA-A*02:06 QSYGFQPTNGV RSYSFRPTYGV 1121 320

Q498R

Reference  YQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPAT
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    YQAGNKPCNGVAGFNCYFPLRSYSFRPTYGVGHQPYRVVVLSFELLHAPAT

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 LQSYGFQPT LRSYSFRPT 339 27414
HLA-A*02:06 YGFQPTNGV YSFRPTYGV 174 10
HLA-A*02:06 SYGFQPTNGV SYSFRPTYGV 3944 455
HLA-A*02:06 LQSYGFQPTNGV LRSYSFRPTYGV 249 2086
HLA-A*02:06 QSYGFQPTNGV RSYSFRPTYGV 1121 320

N501Y

Reference  GSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCG
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    GNKPCNGVAGFNCYFPLRSYSFRPTYGVGHQPYRVVVLSFELLHAPATVCG

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 YGFQPTNGV YSFRPTYGV 174 10
HLA-A*02:06 SYGFQPTNGV SYSFRPTYGV 3944 455
HLA-A*02:06 LQSYGFQPTNGV LRSYSFRPTYGV 249 2086
HLA-A*02:06 QSYGFQPTNGV RSYSFRPTYGV 1121 320

Y505H

Reference  CNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKS
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    CNGVAGFNCYFPLRSYSFRPTYGVGHQPYRVVVLSFELLHAPATVCGPKKS

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 YQPYRVVVL HQPYRVVVL 223 2206
HLA-A*02:06 YQPYRVVVLSFEL HQPYRVVVLSFEL 430 2495

D614G

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

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 DVNCTEVPV GVNCTEVPV 3807 208
HLA-A*02:06 QVAVLYQDV QVAVLYQGV 1312 148
HLA-A*02:06 YQDVNCTEV YQGVNCTEV 17 57
HLA-A*02:06 NQVAVLYQDV NQVAVLYQGV 36 18

H655Y

Reference  TPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNS
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    TPTWRVYSTGSNVFQTRAGCLIGAEYVNNSYECDIPIGAGICASYQTQTKS

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 HVNNSYECDIPI YVNNSYECDIPI 837 92

N856K

Reference  AGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGT
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    AGFIKQYGDCLGDIAARDLICAQKFKGLTVLPPLLTDEMIAQYTSALLAGT

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 AQKFNGLTVL AQKFKGLTVL 85 182

N969K

Reference  ALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQID
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    ALGKLQDVVNHNAQALNTLVKQLSSKFGAISSVLNDIFSRLDKVEAEVQID

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 KQLSSNFGA KQLSSKFGA 62 269
HLA-A*02:06 SNFGAISSV SKFGAISSV 361 1100
HLA-A*02:06 KQLSSNFGAI KQLSSKFGAI 58 159

L981F

Reference  AQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQT
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    AQALNTLVKQLSSKFGAISSVLNDIFSRLDKVEAEVQIDRLITGRLQSLQT

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 SVLNDILSRLDKV SVLNDIFSRLDKV 162 37
HLA-A*02:06 SVLNDILSRL SVLNDIFSRL 206 66

M protein

D3G

Reference  MADSNGTITVEELKKLLEQWNLVIGFLF
           || |||||||||||||||||||||||||
Mutated    MAGSNGTITVEELKKLLEEWNLVIGFLF

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 MADSNGTITV MAGSNGTITV 355 772

Q19E

Reference  MADSNGTITVEELKKLLEQWNLVIGFLFLTWICLLQFAYANRNR
           |||||||||||||||||| |||||||||||||||||||||||||
Mutated    MAGSNGTITVEELKKLLEEWNLVIGFLFLTWICLLQFAYANRNR

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 EQWNLVIGFL EEWNLVIGFL 418 10916
HLA-A*02:06 LLEQWNLVI LLEEWNLVI 1869 487

A63T

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

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 WLLWPVTLA WLLWPVTLT 60 302
HLA-A*02:06 TLACFVLAAV TLTCFVLAAV 16 45
HLA-A*02:06 TLACFVLAA TLTCFVLAA 40 107
HLA-A*02:06 FLWLLWPVTLA FLWLLWPVTLT 495 1240
HLA-A*02:06 LACFVLAAV LTCFVLAAV 51 23

E protein

T9I

Reference  MYSFVSEETGTLIVNSVLLFLAFVVFLLVTLAIL
           |||||||| |||||||||||||||||||||||||
Mutated    MYSFVSEEIGTLIVNSVLLFLAFVVFLLVTLAIL

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 FVSEETGTLI FVSEEIGTLI 423 144
HLA-A*02:06 FVSEETGTL FVSEEIGTL 120 41
HLA-A*02:06 FVSEETGTLIV FVSEEIGTLIV 670 266

NS9b protein

P10S

Reference  MDPKISEMHPALRLVDPQIQLAVTRMENAVGRDQN
           ||||||||| |||||||||||||||||||||||||
Mutated    MDPKISEMHSALRLVDPQIQLAVTRM‑‑‑VGRDQN

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 KISEMHPAL KISEMHSAL 62 310

ENA 27-29 deletion

Reference  DPKISEMHPALRLVDPQIQLAVTRMENAVGRDQNNVGPKVYPIILRLGSPLSL
           |||||||||||||||||||||||||   |||||||||||||||||||||||||
Mutated    DPKISEMHSALRLVDPQIQLAVTRM‑‑‑VGRDQNNVGPKVYPIILRLGSPLSL

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 IQLAVTRMENAV IQLAVTRMV 263 47

NSP4 protein

T492I

Reference  ACCHLAKALNDFSNSGSDVLYQPPQTSITSAVLQ
           ||||||||||||||||||||||||| ||||||||
Mutated    ACCHLAKALNDFSNSGSDVLYQPPQISITSAVLQ

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 QPPQTSITSAV QPPQISITSAV 3097 393
HLA-A*02:06 LYQPPQTSITSAV LYQPPQISITSAV 1485 214
HLA-A*02:06 YQPPQTSITSAV YQPPQISITSAV 156 26

NSP6 protein

LSG 105-107 deletion

Reference  YFNMVYMPASWVMRIMTWLDMVDTSLSGFKLKDCVMYASAVVLLILMTARTVY
           |||||||||||||||||||||||||   |||||||||||||||||||||||||
Mutated    YFNMVYMPASWVMRIMTWLDMVDTS‑‑‑FKLKDCVMYASAVVLLILMTARTVY

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 WLDMVDTSL - 63 -
HLA-A*02:06 MTWLDMVDTSLSGFKL MTWLDMVDTSFKL - 265
HLA-A*02:06 RIMTWLDMVDTSL - 342 -
HLA-A*02:06 LDMVDTSLSGFKL LDMVDTSFKL 12977 187
HLA-A*02:06 WLDMVDTSLSGFKL WLDMVDTSFKL 4589 98

I189V

Reference  MWALIISVTSNYSGVVTTVMFLARGIVFMCVEYCPIFFITGNTLQCIMLVY
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    MWALIISVTSNYSGVVTTVMFLARGVVFMCVEYCPIFFITGNTLQCIMLVY

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:06 TTVMFLARGI TTVMFLARGV 259 49
HLA-A*02:06 TVMFLARGI TVMFLARGV 300 61

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*02:06 FPPTSFGPLV FPLTSFGPLV 3379 73
HLA-A*02:06 FNVLFSTVFPP FNVLFSTVFPL 1609 37
HLA-A*02:06 VLFSTVFPP VLFSTVFPL 368 10
HLA-A*02:06 NVLFSTVFPP NVLFSTVFPL 1611 66
HLA-A*02:06 ANFNVLFSTVFPP ANFNVLFSTVFPL 5191 304
HLA-A*02:06 NFNVLFSTVFPP NFNVLFSTVFPL 4220 274
HLA-A*02:06 FNVLFSTVFPPT FNVLFSTVFPLT 4868 388