Summary

This strain contains 12 protein-level mutations:

  • 1 mutation in Spike protein: D614G
  • 3 mutations in N protein: 203-204 RG->KR, M234I, P279S
  • 1 mutation in NS8 protein: G8R
  • 1 mutation in NS9c protein: G50N
  • 1 mutation in NSP2 protein: K81N
  • 1 mutation in NSP12 protein: P323L
  • 2 mutations in NSP14 protein: P43L, D345Y
  • 1 mutation in NSP15 protein: H337Y
  • 1 mutation in NSP16 protein: R287I

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 1 epitope, while stronger binding was found for 4 entries. There are 268 tight binders for the HLA-A*11:01 in the reference immunopeptidome (IC50 affinity ≤ 50 nM); 1 of them became non-tight binders (0.4%) and 1 novel tight binder appeared (0.4%). To avoid possible divisions by zero, we used + 1 regularization term in denominators when calculating percentages.

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HLA-A*11:01

N protein

203-204 RG->KR

Reference  GGSQASSRSSSRSRNSSRNSTPGSSRGTSPARMAGNGGDAALALLLLDRLNQ
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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

NSP2 protein

K81N

Reference  HEIAWYTERSEKSYELQTPFEIKLAKKFDTFNGECPNFVFPLNSIIKTIQP
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Mutated    HEIAWYTERSEKSYELQTPFEIKLANKFDTFNGECPNFVFPLNSIIKTIQP

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*11:01 QTPFEIKLAK QTPFEIKLAN 43 27290

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

NSP14 protein

D345Y

Reference  ALLADKFPVLHDIGNPKAIKCVPQADVEWKFYDAQPCSDKAYKIEELFYSY
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Mutated    ALLADKFPVLHDIGNPKAIKCVPQAYVEWKFYDAQPCSDKAYKIEELFYSY

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*11:01 CVPQADVEWK CVPQAYVEWK 1760 337