Summary

This strain contains 53 protein-level mutations:

  • 27 mutations in Spike protein: V3G, T19I, G142D, V213G, G339D, S371F, S373P, 375-376 ST->FA, D405N, R408S, K417N, N440K, L452R, 477-478 ST->NK, E484A, F486V, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, N969K
  • 5 mutations in N protein: P13L, ERS 31-33 deletion, P151S, 203-204 RG->KR, S413R
  • 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
  • 2 mutations in NSP1 protein: S135R, KSF 141-143 deletion
  • 2 mutations in NSP3 protein: T24I, G489S
  • 3 mutations in NSP4 protein: L264F, T327I, T492I
  • 1 mutation in NSP5 protein: P132H
  • 1 mutation in NSP6 protein: SGF 106-108 deletion
  • 1 mutation in NSP12 protein: P323L
  • 1 mutation in NSP13 protein: R392C
  • 2 mutations in NSP14 protein: I42V, D301G
  • 1 mutation in NSP15 protein: T112I

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*11:01 and peptides affected by the mutations

Weaker binding was found for 32 epitopes, while stronger binding was found for 24 entries. There are 268 tight binders for the HLA-A*11:01 in the reference immunopeptidome (IC50 affinity ≤ 50 nM); 13 of them became non-tight binders (4.8%) and 5 novel tight binders appeared (1.9%). To avoid possible divisions by zero, we used + 1 regularization term in denominators when calculating percentages.

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HLA-A*11:01

Spike protein

G142D

Reference  LLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCT
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    LLIVNNATNVVIKVCEFQFCNDPFLDVYYHKNNKSWMESEFRVYSSANNCT

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*11:01 GVYYHKNNK DVYYHKNNK 51 1768

S371F

Reference  RFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVY
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    RFASVYAWNRKRISNCVADYSVLYNFAPFFAFKCYGVSPTKLNDLCFTNVY

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*11:01 LYNSASFSTFK LYNFAPFFAFK 43 797
HLA-A*11:01 NSASFSTFK NFAPFFAFK 9 94
HLA-A*11:01 SASFSTFK FAPFFAFK 452 1795
HLA-A*11:01 YNSASFSTFK YNFAPFFAFK 12 38
HLA-A*11:01 VLYNSASFSTFK VLYNFAPFFAFK 22 51

S373P

Reference  ASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYAD
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    ASVYAWNRKRISNCVADYSVLYNFAPFFAFKCYGVSPTKLNDLCFTNVYAD

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*11:01 ASFSTFKCY APFFAFKCY 379 12606
HLA-A*11:01 LYNSASFSTFK LYNFAPFFAFK 43 797
HLA-A*11:01 NSASFSTFK NFAPFFAFK 9 94
HLA-A*11:01 SASFSTFK FAPFFAFK 452 1795
HLA-A*11:01 YNSASFSTFK YNFAPFFAFK 12 38
HLA-A*11:01 VLYNSASFSTFK VLYNFAPFFAFK 22 51

375-376 ST->FA

Reference  VYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFV
           |||||||||||||||||||||||||  |||||||||||||||||||||||||
Mutated    VYAWNRKRISNCVADYSVLYNFAPFFAFKCYGVSPTKLNDLCFTNVYADSFV

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*11:01 STFKCYGVSPTK FAFKCYGVSPTK 25 1030
HLA-A*11:01 ASFSTFKCY APFFAFKCY 379 12606
HLA-A*11:01 LYNSASFSTFK LYNFAPFFAFK 43 797
HLA-A*11:01 FSTFKCYGVSPTK FFAFKCYGVSPTK 426 5482
HLA-A*11:01 NSASFSTFK NFAPFFAFK 9 94
HLA-A*11:01 SASFSTFK FAPFFAFK 452 1795
HLA-A*11:01 YNSASFSTFK YNFAPFFAFK 12 38
HLA-A*11:01 VLYNSASFSTFK VLYNFAPFFAFK 22 51

R408S

Reference  SPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCV
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    SPTKLNDLCFTNVYADSFVIRGNEVSQIAPGQTGNIADYNYKLPDDFTGCV

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*11:01 RQIAPGQTGK SQIAPGQTGN 103 32387

K417N

Reference  FTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLD
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    FTNVYADSFVIRGNEVSQIAPGQTGNIADYNYKLPDDFTGCVIAWNSNKLD

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*11:01 RQIAPGQTGK SQIAPGQTGN 103 32387
HLA-A*11:01 QIAPGQTGK QIAPGQTGN 165 32767

N440K

Reference  TGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFE
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    TGNIADYNYKLPDDFTGCVIAWNSNKLDSKVGGNYNYRYRLFRKSNLKPFE

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*11:01 CVIAWNSNN CVIAWNSNK 24486 26
HLA-A*11:01 GCVIAWNSNN GCVIAWNSNK 32767 94
HLA-A*11:01 TGCVIAWNSNN TGCVIAWNSNK 32767 153
HLA-A*11:01 FTGCVIAWNSNN FTGCVIAWNSNK 32767 408

L452R

Reference  DDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGS
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    DDFTGCVIAWNSNKLDSKVGGNYNYRYRLFRKSNLKPFERDISTEIYQAGN

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*11:01 KVGGNYNYL KVGGNYNYR 16150 194
HLA-A*11:01 LYRLFRKSNLK RYRLFRKSNLK 952 401

477-478 ST->NK

Reference  LYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGV
           |||||||||||||||||||||||||  |||||||||||||||||||||||||
Mutated    RYRLFRKSNLKPFERDISTEIYQAGNKPCNGVAGVNCYFPLQSYGFRPTYGV

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*11:01 STEIYQAGST STEIYQAGNK 30358 67

Q498R

Reference  YQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPAT
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    YQAGNKPCNGVAGVNCYFPLQSYGFRPTYGVGHQPYRVVVLSFELLHAPAT

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*11:01 QSYGFQPTN QSYGFRPTY 22068 301

N501Y

Reference  GSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCG
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    GNKPCNGVAGVNCYFPLQSYGFRPTYGVGHQPYRVVVLSFELLHAPATVCG

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*11:01 QSYGFQPTN QSYGFRPTY 22068 301

N679K

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

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*11:01 CASYQTQTN CASYQTQTK 32767 431
HLA-A*11:01 ASYQTQTNSPR ASYQTQTKSHR 346 1426

P681H

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

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*11:01 ASYQTQTNSPR ASYQTQTKSHR 346 1426

N764K

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

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*11:01 LQYGSFCTQLN LQYGSFCTQLK 32767 191
HLA-A*11:01 YGSFCTQLN YGSFCTQLK 32767 386

N969K

Reference  ALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQID
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    ALGKLQDVVNHNAQALNTLVKQLSSKFGAISSVLNDILSRLDKVEAEVQID

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*11:01 TLVKQLSSN TLVKQLSSK 32767 125
HLA-A*11:01 NTLVKQLSSN NTLVKQLSSK 32767 147

N protein

203-204 RG->KR

Reference  GGSQASSRSSSRSRNSSRNSTPGSSRGTSPARMAGNGGDAALALLLLDRLNQ
           |||||||||||||||||||||||||  |||||||||||||||||||||||||
Mutated    GGSQASSRSSSRSRNSSRNSTPGSSKRTSPARMAGNGGDAALALLLLDRLNQ

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*11:01 SSRNSTPGSSR SSRNSTPGSSK 2231 263

NS9b protein

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*11:01 VTRMENAVGR VTRMVGR 268 -

NSP3 protein

T24I

Reference  APTKVTFGDDTVIEVQGYKSVNITFELDERIDKVLNEKCSAYTVELGTE
           ||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    APTKVTFGDDTVIEVQGYKSVNIIFELDERIDKVLNEKCSAYTVELGTE

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*11:01 ITFELDERIDK IIFELDERIDK 446 1259

G489S

Reference  DAPYIVGDVVQEGVLTAVVIPTKKAGGTTEMLAKALRKVPTDNYITTYPGQ
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    DAPYIVGDVVQEGVLTAVVIPTKKASGTTEMLAKALRKVPTDNYITTYPGQ

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*11:01 AGGTTEMLAK ASGTTEMLAK 1254 37
HLA-A*11:01 KAGGTTEMLAK KASGTTEMLAK 589 203

NSP5 protein

P132H

Reference  QPGQTFSVLACYNGSPSGVYQCAMRPNFTIKGSFLNGSCGSVGFNIDYDCV
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    QPGQTFSVLACYNGSPSGVYQCAMRHNFTIKGSFLNGSCGSVGFNIDYDCV

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*11:01 AMRPNFTIK AMRHNFTIK 175 376
HLA-A*11:01 CAMRPNFTIK CAMRHNFTIK 42 88

NSP6 protein

SGF 106-108 deletion

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

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*11:01 MVDTSLSGFK MVDTSLK 21 -
HLA-A*11:01 TSLSGFKLK TSLKLK 22 -
HLA-A*11:01 MTWLDMVDTSLSGFK MTWLDMVDTSLK - 71
HLA-A*11:01 RIMTWLDMVDTSLSGFK RIMTWLDMVDTSLK - 128
HLA-A*11:01 DTSLSGFKLK DTSLKLK 488 -
HLA-A*11:01 WLDMVDTSLSGFK WLDMVDTSLK 4020 492
HLA-A*11:01 MVDTSLSGFKLK MVDTSLKLK 143 50

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*11:01 PTSFGPLVR LTSFGPLVR 4068 379
HLA-A*11:01 PTSFGPLVRK LTSFGPLVRK 123 21

NSP13 protein

R392C

Reference  TADIVVFDEISMATNYDLSVVNARLRAKHYVYIGDPAQLPAPRTLLTKGTL
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    TADIVVFDEISMATNYDLSVVNARLCAKHYVYIGDPAQLPAPRTLLTKGTL

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*11:01 VVNARLRAK VVNARLCAK 145 44