Summary

This strain contains 24 protein-level mutations:

  • 10 mutations in Spike protein: T19R, K77T, G142D, EF 156-157 deletion, R158G, L452R, T478K, D614G, P681R, D950N
  • 3 mutations in N protein: D63G, R203M, D377Y
  • 1 mutation in M protein: I82T
  • 1 mutation in NS3 protein: S26L
  • 2 mutations in NS7a protein: V82A, T120I
  • 1 mutation in NS9b protein: T60A
  • 1 mutation in NS9c protein: G50W
  • 1 mutation in NSP2 protein: P129L
  • 1 mutation in NSP3 protein: P822L
  • 2 mutations in NSP4 protein: D217N, F375S
  • 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*02:02 and peptides affected by the mutations

Weaker binding was found for 16 epitopes, while stronger binding was found for 37 entries. There are 672 tight binders for the HLA-A*02:02 in the reference immunopeptidome (IC50 affinity ≤ 50 nM); 2 of them became non-tight binders (0.3%) and 14 novel tight binders appeared (2.1%). To avoid possible divisions by zero, we used + 1 regularization term in denominators when calculating percentages.

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HLA-A*02:02

Spike protein

G142D

Reference  LLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCT
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Mutated    LLIVNNATNVVIKVCEFQFCNDPFLDVYYHKNNKSWMES‑‑GVYSSANNCT

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 FCNDPFLGV FCNDPFLDV 365 2187
HLA-A*02:02 EFQFCNDPFLGV EFQFCNDPFLDV 477 1725
HLA-A*02:02 FQFCNDPFLGV FQFCNDPFLDV 45 122

EF 156-157 deletion

Reference  CEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGK
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Mutated    CEFQFCNDPFLDVYYHKNNKSWMES‑‑GVYSSANNCTFEYVSQPFLMDLEGK

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 WMESEFRV WMESGV 320 -
HLA-A*02:02 WMESEFRVYS WMESGVYS 286 11441
HLA-A*02:02 WMESEFRVYSSA WMESGVYSSA 1287 50

R158G

Reference  FQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQ
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Mutated    FQFCNDPFLDVYYHKNNKSWMES‑‑GVYSSANNCTFEYVSQPFLMDLEGKQ

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 WMESEFRV WMESGV 320 -
HLA-A*02:02 WMESEFRVYS WMESGVYS 286 11441
HLA-A*02:02 WMESEFRVYSSA WMESGVYSSA 1287 50

L452R

Reference  DDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGS
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Mutated    DDFTGCVIAWNSNNLDSKVGGNYNYRYRLFRKSNLKPFERDISTEIYQAGS

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 YLYRLFRKSNL YRYRLFRKSNL 188 23354
HLA-A*02:02 KVGGNYNYL KVGGNYNYR 279 23086

T478K

Reference  YRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGV
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Mutated    YRLFRKSNLKPFERDISTEIYQAGSKPCNGVEGFNCYFPLQSYGFQPTNGV

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 YQAGSTPCNGV YQAGSKPCNGV 107 225

D614G

Reference  PCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTG
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Mutated    PCSFGGVSVITPGTNTSNQVAVLYQGVNCTEVPVAIHADQLTPTWRVYSTG

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 DVNCTEVPV GVNCTEVPV 4099 213
HLA-A*02:02 QVAVLYQDV QVAVLYQGV 1107 188
HLA-A*02:02 NQVAVLYQDV NQVAVLYQGV 269 116

D950N

Reference  NQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISS
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Mutated    NQFNSAIGKIQDSLSSTASALGKLQNVVNQNAQALNTLVKQLSSNFGAISS

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 KLQDVVNQNAQAL KLQNVVNQNAQAL 81 266
HLA-A*02:02 KLQDVVNQNAQA KLQNVVNQNAQA 318 989
HLA-A*02:02 KLQDVVNQNA KLQNVVNQNA 129 382

N protein

D63G

Reference  KQRRPQGLPNNTASWFTALTQHGKEDLKFPRGQGVPINTNSSPDDQIGYYR
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Mutated    KQRRPQGLPNNTASWFTALTQHGKEGLKFPRGQGVPINTNSSPDDQIGYYR

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 DLKFPRGQGV GLKFPRGQGV 6781 153

M protein

I82T

Reference  LWPVTLACFVLAAVYRINWITGGIAIAMACLVGLMWLSYFIASFRLFARTR
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Mutated    LWPVTLACFVLAAVYRINWITGGIATAMACLVGLMWLSYFIASFRLFARTR

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 WITGGIAIA WITGGIATA 333 88
HLA-A*02:02 AIAMACLVGL ATAMACLVGL 41 133
HLA-A*02:02 GIAIAMACL GIATAMACL 110 50
HLA-A*02:02 GIAIAMACLV GIATAMACLV 84 39
HLA-A*02:02 GGIAIAMACL GGIATAMACL 596 288

NS9c protein

G50W

Reference  AAVKPLLVPHHVVATVQEIQLQAAVGELLLLEWLAMAVMLLLLCCCLTD
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Mutated    AAVKPLLVPHHVVATVQEIQLQAAVWELLLLEWLAMAVMLLLLCCCLTD

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 QLQAAVGEL QLQAAVWEL 92 8
HLA-A*02:02 LQAAVGEL LQAAVWEL 3894 402
HLA-A*02:02 IQLQAAVGEL IQLQAAVWEL 170 25
HLA-A*02:02 VQEIQLQAAVGEL VQEIQLQAAVWEL 1944 456
HLA-A*02:02 LQAAVGELL LQAAVWELL 44 20
HLA-A*02:02 QLQAAVGELLL QLQAAVWELLL 530 253

NSP2 protein

P129L

Reference  IQPRVEKKKLDGFMGRIRSVYPVASPNECNQMCLSTLMKCDHCGETSWQTG
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Mutated    IQPRVEKKKLDGFMGRIRSVYPVASLNECNQMCLSTLMKCDHCGETSWQTG

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 SPNECNQMCL SLNECNQMCL 19740 19
HLA-A*02:02 SPNECNQMCLSTL SLNECNQMCLSTL 19590 49
HLA-A*02:02 SPNECNQMC SLNECNQMC 32767 353
HLA-A*02:02 FMGRIRSVYPVASP FMGRIRSVYPVASL 3175 135
HLA-A*02:02 SPNECNQMCLSTLM SLNECNQMCLSTLM 4079 383

NSP4 protein

F375S

Reference  TFYLTNDVSFLAHIQWMVMFTPLVPFWITIAYIICISTKHFYWFFSNYLKR
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Mutated    TFYLTNDVSFLAHIQWMVMFTPLVPSWITIAYIICISTKHFYWFFSNYLKR

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 VMFTPLVPF VMFTPLVPS 651 206
HLA-A*02:02 MVMFTPLVPF MVMFTPLVPS 429 146
HLA-A*02:02 TPLVPFWITI TPLVPSWITI 297 757
HLA-A*02:02 FTPLVPFWI FTPLVPSWI 135 344

NSP12 protein

P323L

Reference  CVNCLDDRCILHCANFNVLFSTVFPPTSFGPLVRKIFVDGVPFVVSTGYHF
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Mutated    CVNCLDDRCILHCANFNVLFSTVFPLTSFGPLVRKIFVDGVPFVVSTGYHF

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 FPPTSFGPLV FPLTSFGPLV 7237 18
HLA-A*02:02 NVLFSTVFPP NVLFSTVFPL 1088 17
HLA-A*02:02 FNVLFSTVFPP FNVLFSTVFPL 1014 16
HLA-A*02:02 ANFNVLFSTVFPP ANFNVLFSTVFPL 3126 53
HLA-A*02:02 LFSTVFPP LFSTVFPL 9311 167
HLA-A*02:02 NFNVLFSTVFPP NFNVLFSTVFPL 2542 47
HLA-A*02:02 VLFSTVFPP VLFSTVFPL 269 5
HLA-A*02:02 FNVLFSTVFPPT FNVLFSTVFPLT 4116 110
HLA-A*02:02 FNVLFSTVFPPTS FNVLFSTVFPLTS 10920 497
HLA-A*02:02 FSTVFPPTSFGPLV FSTVFPLTSFGPLV 6958 322
HLA-A*02:02 CANFNVLFSTVFPP CANFNVLFSTVFPL 8183 391
HLA-A*02:02 VLFSTVFPPTS VLFSTVFPLTS 1210 377
HLA-A*02:02 VLFSTVFPPT VLFSTVFPLT 113 44
HLA-A*02:02 TVFPPTSFGPLV TVFPLTSFGPLV 789 343