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*23:01 and peptides affected by the mutations

Weaker binding was found for 8 epitopes, while stronger binding was found for 54 entries. There are 104 tight binders for the HLA-A*23:01 in the reference immunopeptidome (IC50 affinity ≤ 50 nM); 1 of them became non-tight binders (1.0%) and 10 novel tight binders appeared (9.5%). To avoid possible divisions by zero, we used + 1 regularization term in denominators when calculating percentages.

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HLA-A*23:01

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-A*23:01 YYHKNNKSW DHKNNKSW 150 32767
HLA-A*23:01 VYYHKNNKSW DHKNNKSW 230 32767

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*23:01 YYHKNNKSW DHKNNKSW 150 32767
HLA-A*23:01 VYYHKNNKSW DHKNNKSW 230 32767

N211 deletion

Reference  FKNLREFVFKNIDGYFKIYSKHTPINLVR‑‑‑DLPQGFSALEPLVDLPIGI
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    FKNLREFVFKNIDGYFKIYSKHTPI‑IVREPEDLPQGFSALEPLVDLPIGI

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*23:01 IYSKHTPINL IYSKHTPII 345 65

L212I

Reference  KNLREFVFKNIDGYFKIYSKHTPINLVR‑‑‑DLPQGFSALEPLVDLPIGIN
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    KNLREFVFKNIDGYFKIYSKHTPI‑IVREPEDLPQGFSALEPLVDLPIGIN

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*23:01 IYSKHTPINL IYSKHTPII 345 65

S371L

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

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*23:01 VLYNSASFS VLYNLAPFF 32767 117
HLA-A*23:01 LYNSASFS LYNLAPFF 22508 301
HLA-A*23:01 YNSASFSTF YNLAPFFTF 352 23
HLA-A*23:01 DYSVLYNSASFSTF DYSVLYNLAPFFTF 2385 192
HLA-A*23:01 YSVLYNSASFSTF YSVLYNLAPFFTF 1474 248
HLA-A*23:01 SVLYNSASFSTF SVLYNLAPFFTF 656 145
HLA-A*23:01 LYNSASFSTFKC LYNLAPFFTFKC 1642 470
HLA-A*23:01 VLYNSASFSTF VLYNLAPFFTF 133 41
HLA-A*23:01 LYNSASFSTFK LYNLAPFFTFK 265 97
HLA-A*23:01 LYNSASFSTF LYNLAPFFTF 7 3

S373P

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

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*23:01 VLYNSASFS VLYNLAPFF 32767 117
HLA-A*23:01 LYNSASFS LYNLAPFF 22508 301
HLA-A*23:01 YNSASFSTF YNLAPFFTF 352 23
HLA-A*23:01 DYSVLYNSASFSTF DYSVLYNLAPFFTF 2385 192
HLA-A*23:01 YSVLYNSASFSTF YSVLYNLAPFFTF 1474 248
HLA-A*23:01 SVLYNSASFSTF SVLYNLAPFFTF 656 145
HLA-A*23:01 LYNSASFSTFKC LYNLAPFFTFKC 1642 470
HLA-A*23:01 VLYNSASFSTF VLYNLAPFFTF 133 41
HLA-A*23:01 LYNSASFSTFK LYNLAPFFTFK 265 97
HLA-A*23:01 LYNSASFSTF LYNLAPFFTF 7 3

S375F

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

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*23:01 VLYNSASFS VLYNLAPFF 32767 117
HLA-A*23:01 LYNSASFS LYNLAPFF 22508 301
HLA-A*23:01 YNSASFSTF YNLAPFFTF 352 23
HLA-A*23:01 DYSVLYNSASFSTF DYSVLYNLAPFFTF 2385 192
HLA-A*23:01 YSVLYNSASFSTF YSVLYNLAPFFTF 1474 248
HLA-A*23:01 SVLYNSASFSTF SVLYNLAPFFTF 656 145
HLA-A*23:01 LYNSASFSTFKC LYNLAPFFTFKC 1642 470
HLA-A*23:01 VLYNSASFSTF VLYNLAPFFTF 133 41
HLA-A*23:01 LYNSASFSTFK LYNLAPFFTFK 265 97
HLA-A*23:01 LYNSASFSTF LYNLAPFFTF 7 3

Q493R

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

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*23:01 CYFPLQSYGFQ CYFPLRSYSFR 498 191
HLA-A*23:01 NCYFPLQSYGF NCYFPLRSYSF 271 112
HLA-A*23:01 FNCYFPLQSYGF FNCYFPLRSYSF 795 334
HLA-A*23:01 YFPLQSYGF YFPLRSYSF 49 24

G496S

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

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*23:01 SYGFQPTNGV SYSFRPTYGV 2697 488
HLA-A*23:01 CYFPLQSYGFQ CYFPLRSYSFR 498 191
HLA-A*23:01 NCYFPLQSYGF NCYFPLRSYSF 271 112
HLA-A*23:01 FNCYFPLQSYGF FNCYFPLRSYSF 795 334
HLA-A*23:01 YFPLQSYGF YFPLRSYSF 49 24

Q498R

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

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*23:01 SYGFQPTNGV SYSFRPTYGV 2697 488
HLA-A*23:01 CYFPLQSYGFQ CYFPLRSYSFR 498 191

N501Y

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

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*23:01 SYGFQPTNGV SYSFRPTYGV 2697 488

Y505H

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

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*23:01 GYQPYRVVVLSF GHQPYRVVVLSF 107 3241
HLA-A*23:01 YQPYRVVVLSF HQPYRVVVLSF 465 1280

D796Y

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

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*23:01 KDFGGFNF KYFGGFNF 15419 23
HLA-A*23:01 KDFGGFNFSQI KYFGGFNFSQI 15932 37
HLA-A*23:01 KDFGGFNFSQIL KYFGGFNFSQIL 15831 63
HLA-A*23:01 DFGGFNFSQI YFGGFNFSQI 5424 461
HLA-A*23:01 IYKTPPIKDF IYKTPPIKYF 273 98

M protein

Q19E

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

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*23:01 QWNLVIGFLF EWNLVIGFLF 18 79

A63T

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

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*23:01 LWPVTLACF LWPVTLTCF 57 155

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*23:01 MYSFVSEET MYSFVSEEI 5604 31

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*23:01 VLYQPPQTSI VLYQPPQISI 979 462
HLA-A*23:01 LYQPPQTSI LYQPPQISI 278 132

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*23:01 TWLDMVDTSLSGF TWLDMVDTSF 387 34

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*23:01 LFSTVFPPTSF LFSTVFPLTSF 370 179