Summary

This strain contains 20 protein-level mutations:

  • 8 mutations in Spike protein: Q52R, A67V, HV 69-70 deletion, Y144 deletion, E484K, D614G, Q677H, F888L
  • 4 mutations in N protein: S2 deletion, D3Y, A12G, T205I
  • 1 mutation in M protein: I82T
  • 1 mutation in E protein: L21F
  • 1 mutation in NS6 protein: F2 deletion
  • 1 mutation in NS9b protein: H9D
  • 1 mutation in NS9c protein: L52F
  • 1 mutation in NSP3 protein: T1189I
  • 1 mutation in NSP6 protein: SGF 106-108 deletion
  • 1 mutation in NSP12 protein: P323F

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 33 epitopes, while stronger binding was found for 31 entries. There are 672 tight binders for the HLA-A*02:02 in the reference immunopeptidome (IC50 affinity ≤ 50 nM); 9 of them became non-tight binders (1.3%) and 8 novel tight binders appeared (1.2%). To avoid possible divisions by zero, we used + 1 regularization term in denominators when calculating percentages.

Download figure  Export data to csv 
HLA-A*02:02

Spike protein

A67V

Reference  VFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYF
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    VFRSSVLHSTRDLFLPFFSNVTWFHVI‑‑SGTNGTKRFDNPVLPFNDGVYF

Export table to csv 
Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 VTWFHAIHV VTWFHVI 369 -
HLA-A*02:02 NVTWFHAIHV NVTWFHVI 468 14619
HLA-A*02:02 FSNVTWFHA FSNVTWFHV 741 115
HLA-A*02:02 FFSNVTWFHA FFSNVTWFHV 328 79
HLA-A*02:02 FLPFFSNVTWFHA FLPFFSNVTWFHV 117 32
HLA-A*02:02 FLPFFSNVTWFHAI FLPFFSNVTWFHVI 151 392

HV 69-70 deletion

Reference  RSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFAST
           |||||||||||||||||||||||||  |||||||||||||||||||||||||
Mutated    RSSVLHSTRDLFLPFFSNVTWFHVI‑‑SGTNGTKRFDNPVLPFNDGVYFAST

Export table to csv 
Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 VTWFHAIHV VTWFHVI 369 -
HLA-A*02:02 NVTWFHAIHV NVTWFHVI 468 14619

D614G

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

Export table to csv 
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

F888L

Reference  PLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQ
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    PLLTDEMIAQYTSALLAGTITSGWTLGAGAALQIPFAMQMAYRFNGIGVTQ

Export table to csv 
Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 LLAGTITSGWTF LLAGTITSGWTL 2639 26
HLA-A*02:02 ALLAGTITSGWTF ALLAGTITSGWTL 7387 110
HLA-A*02:02 TFGAGAALQI TLGAGAALQI 7571 192
HLA-A*02:02 LLAGTITSGWTFG LLAGTITSGWTLG 3915 444
HLA-A*02:02 ITSGWTFGA ITSGWTLGA 257 1444
HLA-A*02:02 WTFGAGAAL WTLGAGAAL 146 473

M protein

I82T

Reference  LWPVTLACFVLAAVYRINWITGGIAIAMACLVGLMWLSYFIASFRLFARTR
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    LWPVTLACFVLAAVYRINWITGGIATAMACLVGLMWLSYFIASFRLFARTR

Export table to csv 
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

E protein

L21F

Reference  MYSFVSEETGTLIVNSVLLFLAFVVFLLVTLAILTALRLCAYCCNI
           |||||||||||||||||||| |||||||||||||||||||||||||
Mutated    MYSFVSEETGTLIVNSVLLFFAFVVFLLVTLAILTALRLCAYCCNI

Export table to csv 
Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 FLAFVVFL FFAFVVFL 24 3923
HLA-A*02:02 IVNSVLLFL IVNSVLLFF 25 3332
HLA-A*02:02 LIVNSVLLFL LIVNSVLLFF 70 5517
HLA-A*02:02 LFLAFVVFLL LFFAFVVFLL 16 1201
HLA-A*02:02 FLAFVVFLLVTL FFAFVVFLLVTL 36 2659
HLA-A*02:02 FLAFVVFLLV FFAFVVFLLV 12 792
HLA-A*02:02 FLAFVVFLLVTLAI FFAFVVFLLVTLAI 185 10954
HLA-A*02:02 TLIVNSVLLFL TLIVNSVLLFF 147 7129
HLA-A*02:02 FLAFVVFLL FFAFVVFLL 3 125
HLA-A*02:02 FLAFVVFLLVT FFAFVVFLLVT 334 13428
HLA-A*02:02 FLAFVVFLLVTLA FFAFVVFLLVTLA 101 3916
HLA-A*02:02 LFLAFVVFLLV LFFAFVVFLLV 427 7784
HLA-A*02:02 LFLAFVVFLLVTL LFFAFVVFLLVTL 399 6794
HLA-A*02:02 SVLLFLAFVVFLL SVLLFFAFVVFLL 157 1091
HLA-A*02:02 LAFVVFLLV FAFVVFLLV 1446 408
HLA-A*02:02 VLLFLAFVVFL VLLFFAFVVFL 934 457

NS6 protein

F2 deletion

Reference  MFHLVDFQVTIAEILLIIMRTFKVSIW
           | |||||||||||||||||||||||||
Mutated    M‑HLVDFQVTIAEILLIIMRTFKVSIW

Export table to csv 
Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 FHLVDFQVTI - 9 -
HLA-A*02:02 FHLVDFQVTIA - 411 -
HLA-A*02:02 MFHLVDFQV MHLVDFQV 403 3464
HLA-A*02:02 MFHLVDFQVTI MHLVDFQVTI 51 11

NS9c protein

L52F

Reference  VKPLLVPHHVVATVQEIQLQAAVGELLLLEWLAMAVMLLLLCCCLTD
           ||||||||||||||||||||||||| |||||||||||||||||||||
Mutated    VKPLLVPHHVVATVQEIQLQAAVGEFLLLEWLAMAVMLLLLCCCLTD

Export table to csv 
Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 QLQAAVGEL QLQAAVGEF 92 2789
HLA-A*02:02 IQLQAAVGEL IQLQAAVGEF 170 4413
HLA-A*02:02 LLLLEWLAM FLLLEWLAM 1379 150
HLA-A*02:02 LLLLEWLA FLLLEWLA 2866 389
HLA-A*02:02 LLLLEWLAMA FLLLEWLAMA 67 13
HLA-A*02:02 LLLLEWLAMAVMLL FLLLEWLAMAVMLL 714 164
HLA-A*02:02 LLLLEWLAMAV FLLLEWLAMAV 453 147
HLA-A*02:02 QLQAAVGELLL QLQAAVGEFLL 530 186
HLA-A*02:02 LQAAVGELLL LQAAVGEFLL 100 42

NSP6 protein

SGF 106-108 deletion

Reference  FNMVYMPASWVMRIMTWLDMVDTSLSGFKLKDCVMYASAVVLLILMTARTVYD
           |||||||||||||||||||||||||   |||||||||||||||||||||||||
Mutated    FNMVYMPASWVMRIMTWLDMVDTSL‑‑‑KLKDCVMYASAVVLLILMTARTVYD

Export table to csv 
Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 FKLKDCVMYA - 8 -
HLA-A*02:02 SGFKLKDCVMYA - 126 -
HLA-A*02:02 MTWLDMVDTSLSGFKL MTWLDMVDTSLKL - 202
HLA-A*02:02 GFKLKDCVMYA - 239 -
HLA-A*02:02 TSLSGFKLKDCVMYA TSLKLKDCVMYA - 244
HLA-A*02:02 WLDMVDTSLS - 441 -
HLA-A*02:02 LDMVDTSLSGFKL LDMVDTSLKL 9971 106
HLA-A*02:02 SLSGFKLKDCV SLKLKDCV 408 10216
HLA-A*02:02 LSGFKLKDCVMYA LKLKDCVMYA 305 28
HLA-A*02:02 WLDMVDTSLSGFKL WLDMVDTSLKL 788 116
HLA-A*02:02 SLSGFKLKDCVMYA SLKLKDCVMYA 55 171

NSP12 protein

P323F

Reference  CVNCLDDRCILHCANFNVLFSTVFPPTSFGPLVRKIFVDGVPFVVSTGYHF
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    CVNCLDDRCILHCANFNVLFSTVFPFTSFGPLVRKIFVDGVPFVVSTGYHF

Export table to csv 
Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*02:02 TVFPPTSFGPLV TVFPFTSFGPLV 789 137
HLA-A*02:02 VLFSTVFPP VLFSTVFPF 269 106