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-B*15:03 and peptides affected by the mutations

Weaker binding was found for 24 epitopes, while stronger binding was found for 29 entries. There are 473 tight binders for the HLA-B*15:03 in the reference immunopeptidome (IC50 affinity ≤ 50 nM); 6 of them became non-tight binders (1.3%) and 6 novel tight binders appeared (1.3%). To avoid possible divisions by zero, we used + 1 regularization term in denominators when calculating percentages.

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HLA-B*15:03

Spike protein

T19R

Reference  MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFR
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Mutated    MFVFLVLLPLVSSQCVNLRTRTQLPPAYTNSFTRGVYYPDKVFR

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-B*15:03 TTRTQLPPAY RTRTQLPPAY 888 198

K77T

Reference  QDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIR
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Mutated    QDLFLPFFSNVTWFHAIHVSGTNGTTRFDNPVLPFNDGVYFASTEKSNIIR

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-B*15:03 TKRFDNPVL TTRFDNPVL 162 3746
HLA-B*15:03 TKRFDNPVLPF TTRFDNPVLPF 100 750

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-B*15:03 WMESEFRVY WMESGVY 10 -
HLA-B*15:03 NKSWMESEF NKSWMES 126 -
HLA-B*15:03 MESEFRVY MESGVY 180 -
HLA-B*15:03 HKNNKSWMESEFRVY HKNNKSWMESGVY - 224
HLA-B*15:03 YHKNNKSWMESEFRVY YHKNNKSWMESGVY - 418
HLA-B*15:03 KSWMESEFRVY KSWMESGVY 250 9
HLA-B*15:03 NKSWMESEFRVY NKSWMESGVY 1077 62
HLA-B*15:03 SWMESEFRVY SWMESGVY 196 1469
HLA-B*15:03 EFRVYSSANNCTF GVYSSANNCTF 1751 469
HLA-B*15:03 FRVYSSANNCTF GVYSSANNCTF 131 469

R158G

Reference  FQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQ
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    FQFCNDPFLDVYYHKNNKSWMES‑‑GVYSSANNCTFEYVSQPFLMDLEGKQ

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-B*15:03 WMESEFRVY WMESGVY 10 -
HLA-B*15:03 MESEFRVY MESGVY 180 -
HLA-B*15:03 HKNNKSWMESEFRVY HKNNKSWMESGVY - 224
HLA-B*15:03 YHKNNKSWMESEFRVY YHKNNKSWMESGVY - 418
HLA-B*15:03 KSWMESEFRVY KSWMESGVY 250 9
HLA-B*15:03 NKSWMESEFRVY NKSWMESGVY 1077 62
HLA-B*15:03 RVYSSANNCTF GVYSSANNCTF 41 469
HLA-B*15:03 RVYSSANNCTFEY GVYSSANNCTFEY 203 2038
HLA-B*15:03 SWMESEFRVY SWMESGVY 196 1469
HLA-B*15:03 EFRVYSSANNCTF GVYSSANNCTF 1751 469
HLA-B*15:03 FRVYSSANNCTF GVYSSANNCTF 131 469

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-B*15:03 SKVGGNYNYLY SKVGGNYNYRY 313 720

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-B*15:03 YQAGSTPCNGVEGF YQAGSKPCNGVEGF 217 656

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-B*15:03 TQHGKEDLKF TQHGKEGLKF 206 56

R203M

Reference  GGSQASSRSSSRSRNSSRNSTPGSSRGTSPARMAGNGGDAALALLLLDRLN
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    GGSQASSRSSSRSRNSSRNSTPGSSMGTSPARMAGNGGDAALALLLLDRLN

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-B*15:03 RNSTPGSSR RNSTPGSSM 16125 70
HLA-B*15:03 SRNSTPGSSR SRNSTPGSSM 25421 299
HLA-B*15:03 SRGTSPARM SMGTSPARM 2669 248
HLA-B*15:03 SSRGTSPARM SSMGTSPARM 1402 217

D377Y

Reference  LLNKHIDAYKTFPPTEPKKDKKKKADETQALPQRQKKQQTVTLLPAADLDD
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Mutated    LLNKHIDAYKTFPPTEPKKDKKKKAYETQALPQRQKKQQTVTLLPAADLDD

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-B*15:03 KKADETQAL KKAYETQAL 48 18
HLA-B*15:03 KKKADETQAL KKKAYETQAL 560 253

NS3 protein

S26L

Reference  MDLFMRIFTIGTVTLKQGEIKDATPSDFVRATATIPIQASLPFGWLIVGVA
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Mutated    MDLFMRIFTIGTVTLKQGEIKDATPLDFVRATATIPIQASLPFGWLIVGVA

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-B*15:03 KQGEIKDATPS KQGEIKDATPL 9550 310
HLA-B*15:03 GEIKDATPS GEIKDATPL 11520 472

NS9b protein

T60A

Reference  NNVGPKVYPIILRLGSPLSLNMARKTLNSLEDKAFQLTPIAVQMTKLATTE
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    NNVGPKVYPIILRLGSPLSLNMARKALNSLEDKAFQLTPIAVQMTKLATTE

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-B*15:03 RKTLNSLEDKAF RKALNSLEDKAF 83 31

NSP2 protein

P129L

Reference  IQPRVEKKKLDGFMGRIRSVYPVASPNECNQMCLSTLMKCDHCGETSWQTG
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    IQPRVEKKKLDGFMGRIRSVYPVASLNECNQMCLSTLMKCDHCGETSWQTG

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-B*15:03 RSVYPVASP RSVYPVASL 5293 84
HLA-B*15:03 PNECNQMCLSTLM LNECNQMCLSTLM 9595 269

NSP3 protein

P822L

Reference  GKTFYVLPNDDTLRVEAFEYYHTTDPSFLGRYMSALNHTKKWKYPQVNGLT
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    GKTFYVLPNDDTLRVEAFEYYHTTDLSFLGRYMSALNHTKKWKYPQVNGLT

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-B*15:03 FEYYHTTDP FEYYHTTDL 5699 46
HLA-B*15:03 YHTTDPSF YHTTDLSF 1219 446
HLA-B*15:03 YYHTTDPSF YYHTTDLSF 77 34

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-B*15:03 MVMFTPLVPF MVMFTPLVPS 5 1507
HLA-B*15:03 IQWMVMFTPLVPF IQWMVMFTPLVPS 27 6363
HLA-B*15:03 VMFTPLVPF VMFTPLVPS 2 342
HLA-B*15:03 WMVMFTPLVPF WMVMFTPLVPS 54 8157
HLA-B*15:03 QWMVMFTPLVPF QWMVMFTPLVPS 128 14472
HLA-B*15:03 HIQWMVMFTPLVPF HIQWMVMFTPLVPS 153 16597
HLA-B*15:03 MFTPLVPF MFTPLVPS 175 16680
HLA-B*15:03 MVMFTPLVPFW MVMFTPLVPSW 362 2119
HLA-B*15:03 VMFTPLVPFW VMFTPLVPSW 96 234

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-B*15:03 VLFSTVFPP VLFSTVFPL 3115 36