Summary

This strain contains 49 protein-level mutations:

  • 26 mutations in Spike protein: 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
  • 4 mutations in N protein: P13L, R32C, 203-204 RG->KR, S413R
  • 3 mutations in M protein: D3N, Q19E, A63T
  • 1 mutation in E protein: T9I
  • 1 mutation in NS3 protein: T223I
  • 1 mutation in NS9b protein: P10S
  • 1 mutation in NS9c protein: G50N
  • 1 mutation in NSP1 protein: S135R
  • 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: F108L
  • 1 mutation in NSP12 protein: P323L
  • 2 mutations in NSP13 protein: R392C, T481M
  • 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-B*53:01 and peptides affected by the mutations

Weaker binding was not found, while stronger binding was found for 3 entries. There are 41 tight binders for the HLA-B*53:01 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-B*53:01

Spike protein

Q498R

Reference  YQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPAT
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Mutated    YQAGNKPCNGVAGVNCYFPLQSYGFRPTYGVGHQPYRVVVLSFELLHAPAT

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-B*53:01 FPLQSYGFQPTN FPLQSYGFRPTY 8451 351

N501Y

Reference  GSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCG
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Mutated    GNKPCNGVAGVNCYFPLQSYGFRPTYGVGHQPYRVVVLSFELLHAPATVCG

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-B*53:01 FPLQSYGFQPTN FPLQSYGFRPTY 8451 351

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*53:01 FPPTSFGPL FPLTSFGPL 3581 154