Summary

This strain contains 46 protein-level mutations:

  • 29 mutations in Spike protein: A67V, HV 69-70 deletion, T95I, GVY 142-144 deletion, Y145D, N211 deletion, L212I, G339D, S371F, S373P, S375F, D405N, K417T, N440K, G446S, 477-478 ST->NK, E484A, Q493R, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, N969K
  • 3 mutations in N protein: P13L, ERS 31-33 deletion, 203-204 RG->KR
  • 2 mutations in M protein: Q19E, A63T
  • 1 mutation in E protein: T9I
  • 1 mutation in NS3 protein: T223I
  • 2 mutations in NS9b protein: P10S, ENA 27-29 deletion
  • 1 mutation in NS9c protein: G50N
  • 1 mutation in NSP1 protein: S135R
  • 2 mutations in NSP4 protein: T327I, T492I
  • 1 mutation in NSP5 protein: P132H
  • 1 mutation in NSP6 protein: A88V
  • 2 mutations in NSP12 protein: R249M, 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-C*14:02 and peptides affected by the mutations

Weaker binding was found for 26 epitopes, while stronger binding was found for 43 entries. There are 196 tight binders for the HLA-C*14:02 in the reference immunopeptidome (IC50 affinity ≤ 50 nM); 7 of them became non-tight binders (3.6%) and 7 novel tight binders appeared (3.6%). To avoid possible divisions by zero, we used + 1 regularization term in denominators when calculating percentages.

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HLA-C*14:02

Spike protein

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-C*14:02 YYHKNNKSWM DHKNNKSWM 19 12782
HLA-C*14:02 YYHKNNKSW DHKNNKSW 52 32767
HLA-C*14:02 YYHKNNKSWMESEF DHKNNKSWMESEF 227 28734
HLA-C*14:02 VYYHKNNKSWM DHKNNKSWM 327 12782

Y145D

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

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*14:02 YYHKNNKSWM DHKNNKSWM 19 12782
HLA-C*14:02 YYHKNNKSW DHKNNKSW 52 32767
HLA-C*14:02 YYHKNNKSWMESEF DHKNNKSWMESEF 227 28734
HLA-C*14:02 VYYHKNNKSWM DHKNNKSWM 327 12782
HLA-C*14:02 YHKNNKSWM DHKNNKSWM 392 12782

N211 deletion

Reference  FKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINIT
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    FKNLREFVFKNIDGYFKIYSKHTPI‑IVRDLPQGFSALEPLVDLPIGINIT

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*14:02 IYSKHTPINL IYSKHTPII 139 44

L212I

Reference  KNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITR
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    KNLREFVFKNIDGYFKIYSKHTPI‑IVRDLPQGFSALEPLVDLPIGINITR

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*14:02 IYSKHTPINL IYSKHTPII 139 44

S371F

Reference  RFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVY
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    RFASVYAWNRKRISNCVADYSVLYNFAPFFTFKCYGVSPTKLNDLCFTNVY

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*14:02 LYNSASFS LYNFAPFF 5693 117
HLA-C*14:02 VLYNSASFS VLYNFAPFF 11085 354
HLA-C*14:02 NSASFSTF NFAPFFTF 2544 153
HLA-C*14:02 LYNSASFSTF LYNFAPFFTF 20 99

S373P

Reference  ASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYAD
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    ASVYAWNRKRISNCVADYSVLYNFAPFFTFKCYGVSPTKLNDLCFTNVYAD

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*14:02 LYNSASFS LYNFAPFF 5693 117
HLA-C*14:02 VLYNSASFS VLYNFAPFF 11085 354
HLA-C*14:02 NSASFSTF NFAPFFTF 2544 153
HLA-C*14:02 SFSTFKCY PFFTFKCY 386 6068
HLA-C*14:02 LYNSASFSTF LYNFAPFFTF 20 99

S375F

Reference  VYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSF
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    VYAWNRKRISNCVADYSVLYNFAPFFTFKCYGVSPTKLNDLCFTNVYADSF

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*14:02 LYNSASFS LYNFAPFF 5693 117
HLA-C*14:02 VLYNSASFS VLYNFAPFF 11085 354
HLA-C*14:02 NSASFSTF NFAPFFTF 2544 153
HLA-C*14:02 SFSTFKCY PFFTFKCY 386 6068
HLA-C*14:02 LYNSASFSTF LYNFAPFFTF 20 99

D405N

Reference  YGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFT
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    YGVSPTKLNDLCFTNVYADSFVIRGNEVRQIAPGQTGTIADYNYKLPDDFT

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*14:02 SFVIRGDEV SFVIRGNEV 216 46

477-478 ST->NK

Reference  LYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGV
           |||||||||||||||||||||||||  |||||||||||||||||||||||||
Mutated    LYRLFRKSNLKPFERDISTEIYQAGNKPCNGVAGFNCYFPLRSYGFRPTYGV

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*14:02 IYQAGSTPC IYQAGNKPC 134 459

Q493R

Reference  ISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELL
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    ISTEIYQAGNKPCNGVAGFNCYFPLRSYGFRPTYGVGHQPYRVVVLSFELL

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*14:02 YFPLQSYGFQPTN YFPLRSYGFRPTY 18230 74
HLA-C*14:02 QSYGFQPTN RSYGFRPTY 25941 110
HLA-C*14:02 CYFPLQSYGFQPTN CYFPLRSYGFRPTY 24158 394

Q498R

Reference  YQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPAT
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    YQAGNKPCNGVAGFNCYFPLRSYGFRPTYGVGHQPYRVVVLSFELLHAPAT

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*14:02 SYGFQPTN SYGFRPTY 20230 66
HLA-C*14:02 YFPLQSYGFQPTN YFPLRSYGFRPTY 18230 74
HLA-C*14:02 QSYGFQPTN RSYGFRPTY 25941 110
HLA-C*14:02 CYFPLQSYGFQPTN CYFPLRSYGFRPTY 24158 394
HLA-C*14:02 FQPTNGVGYQPY FRPTYGVGHQPY 3107 366

N501Y

Reference  GSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCG
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    GNKPCNGVAGFNCYFPLRSYGFRPTYGVGHQPYRVVVLSFELLHAPATVCG

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*14:02 TNGVGYQPY TYGVGHQPY 5468 16
HLA-C*14:02 SYGFQPTN SYGFRPTY 20230 66
HLA-C*14:02 YFPLQSYGFQPTN YFPLRSYGFRPTY 18230 74
HLA-C*14:02 QSYGFQPTN RSYGFRPTY 25941 110
HLA-C*14:02 CYFPLQSYGFQPTN CYFPLRSYGFRPTY 24158 394
HLA-C*14:02 FQPTNGVGYQPY FRPTYGVGHQPY 3107 366

Y505H

Reference  CNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKS
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    CNGVAGFNCYFPLRSYGFRPTYGVGHQPYRVVVLSFELLHAPATVCGPKKS

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*14:02 TNGVGYQPY TYGVGHQPY 5468 16
HLA-C*14:02 GYQPYRVVV GHQPYRVVV 78 3539
HLA-C*14:02 GYQPYRVVVL GHQPYRVVVL 213 4430
HLA-C*14:02 VGYQPYRVVV VGHQPYRVVV 413 7561
HLA-C*14:02 FQPTNGVGYQPY FRPTYGVGHQPY 3107 366
HLA-C*14:02 YQPYRVVVL HQPYRVVVL 102 347

N679K

Reference  EHVNNSYECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLGAENS
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    EYVNNSYECDIPIGAGICASYQTQTKSHRRARSVASQSIIAYTMSLGAENS

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*14:02 SYQTQTNSP SYQTQTKSH 3691 214

P681H

Reference  VNNSYECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLGAENSVA
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    VNNSYECDIPIGAGICASYQTQTKSHRRARSVASQSIIAYTMSLGAENSVA

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*14:02 SYQTQTNSP SYQTQTKSH 3691 214

N764K

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

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*14:02 SFCTQLNRAL SFCTQLKRAL 234 511

D796Y

Reference  AVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDL
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    AVEQDKNTQEVFAQVKQIYKTPPIKYFGGFNFSQILPDPSKPSKRSFIEDL

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*14:02 IYKTPPIKD IYKTPPIKY 16538 55
HLA-C*14:02 KDFGGFNF KYFGGFNF 22081 90
HLA-C*14:02 KDFGGFNFSQIL KYFGGFNFSQIL 14873 165
HLA-C*14:02 DFGGFNFSQIL YFGGFNFSQIL 6960 139
HLA-C*14:02 IYKTPPIKDF IYKTPPIKYF 341 158

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-C*14:02 MYSFVSEET MYSFVSEEI 901 30

NSP4 protein

T327I

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

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*14:02 LFLMSFTVL LFLMSFIVL 18 112
HLA-C*14:02 FLMSFTVL FLMSFIVL 475 2138

NSP6 protein

A88V

Reference  KHAFLCLFLLPSLATVAYFNMVYMPASWVMRIMTWLDMVDTSLSGFKLKDC
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    KHAFLCLFLLPSLATVAYFNMVYMPVSWVMRIMTWLDMVDTSLSGFKLKDC

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*14:02 YFNMVYMPA YFNMVYMPV 154 33
HLA-C*14:02 AYFNMVYMPA AYFNMVYMPV 1096 243
HLA-C*14:02 FNMVYMPASWVM FNMVYMPVSWVM 72 205
HLA-C*14:02 YFNMVYMPASWVM YFNMVYMPVSWVM 57 136

NSP12 protein

R249M

Reference  QTTPGSGVPVVDSYYSLLMPILTLTRALTAESHVDTDLTKPYIKWDLLKYD
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    QTTPGSGVPVVDSYYSLLMPILTLTMALTAESHVDTDLTKPYIKWDLLKYD

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*14:02 SYYSLLMPILTLTR SYYSLLMPILTLTM 8532 128
HLA-C*14:02 LMPILTLTR LMPILTLTM 7220 123
HLA-C*14:02 YYSLLMPILTLTR YYSLLMPILTLTM 8631 191

P323L

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

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*14:02 VLFSTVFPP VLFSTVFPL 21407 220
HLA-C*14:02 LFSTVFPP LFSTVFPL 11979 138
HLA-C*14:02 LFSTVFPPTSF LFSTVFPLTSF 396 950
HLA-C*14:02 VFPPTSFGPL VFPLTSFGPL 47 99