Summary

This strain contains 11 protein-level mutations:

  • 4 mutations in Spike protein: S13I, W152C, L452R, D614G
  • 1 mutation in N protein: T205I
  • 2 mutations in NS3 protein: Q57H, A99V
  • 1 mutation in NS9c protein: L52F
  • 1 mutation in NSP2 protein: T85I
  • 1 mutation in NSP12 protein: P323L
  • 1 mutation in NSP13 protein: D260Y

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-C*03:02 and peptides affected by the mutations

Weaker binding was found for 1 epitope, while stronger binding was found for 9 entries. There are 198 tight binders for the HLA-C*03:02 in the reference immunopeptidome (IC50 affinity ≤ 50 nM); 0 of them became non-tight binders (0.0%) and 0 novel tight binders appeared (0.0%). To avoid possible divisions by zero, we used + 1 regularization term in denominators when calculating percentages.

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HLA-C*03:02

Spike protein

W152C

Reference  VIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLM
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Mutated    VIKVCEFQFCNDPFLGVYYHKNNKSCMESEFRVYSSANNCTFEYVSQPFLM

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*03:02 WMESEFRVY CMESEFRVY 80 398

NS3 protein

Q57H

Reference  TATIPIQASLPFGWLIVGVALLAVFQSASKIITLKKRWQLALSKGVHFVCN
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Mutated    TATIPIQASLPFGWLIVGVALLAVFHSASKIITLKKRWQLALSKGVHFVCN

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*03:02 QSASKIITL HSASKIITL 724 94

A99V

Reference  SKGVHFVCNLLLLFVTVYSHLLLVAAGLEAPFLYLYALVYFLQSINFVRII
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Mutated    SKGVHFVCNLLLLFVTVYSHLLLVAVGLEAPFLYLYALVYFLQSINFVRII

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*03:02 YSHLLLVAA YSHLLLVAV 683 220

NS9c protein

L52F

Reference  VKPLLVPHHVVATVQEIQLQAAVGELLLLEWLAMAVMLLLLCCCLTD
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Mutated    VKPLLVPHHVVATVQEIQLQAAVGEFLLLEWLAMAVMLLLLCCCLTD

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*03:02 LLLLEWLAM FLLLEWLAM 2566 358
HLA-C*03:02 AAVGELLLL AAVGEFLLL 269 116

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-C*03:02 VLFSTVFPP VLFSTVFPL 20533 273
HLA-C*03:02 FPPTSFGPL FPLTSFGPL 960 313

NSP13 protein

D260Y

Reference  LSAPTLVPQEHYVRITGLYPTLNISDEFSSNVANYQKVGMQKYSTLQGPPG
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Mutated    LSAPTLVPQEHYVRITGLYPTLNISYEFSSNVANYQKVGMQKYSTLQGPPG

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-C*03:02 ISDEFSSNV ISYEFSSNV 1748 134