Summary

This strain contains 70 protein-level mutations:

  • 36 mutations in Spike protein: T19I, L24S, A27S, V83A, G142D, H146Q, E180V, Q183E, V213E, G339H, R346T, L368I, S371F, S373P, 375-376 ST->FA, D405N, R408S, K417N, N440K, 445-446 VG->PS, N460K, 477-478 ST->NR, E484A, F486P, F490S, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, N969K
  • 4 mutations in N protein: P13L, S33G, 203-204 RG->KR, S413R
  • 2 mutations in M protein: Q19E, A63T
  • 2 mutations in E protein: T9I, T11A
  • 1 mutation in NS3 protein: T223I
  • 1 mutation in NS8 protein: G8stop
  • 4 mutations in NS9b protein: I5T, P10S, E27V, N55S
  • 1 mutation in NS9c protein: G50N
  • 2 mutations in NSP1 protein: K47R, S135R
  • 2 mutations in NSP3 protein: T24I, G489S
  • 4 mutations in NSP4 protein: L264F, T327I, L438F, T492I
  • 1 mutation in NSP5 protein: P132H
  • 2 mutations in NSP6 protein: 106-108 SGF->TSL, L260F
  • 2 mutations in NSP12 protein: P323L, G671S
  • 2 mutations in NSP13 protein: S36P, R392C
  • 3 mutations in NSP14 protein: I42V, L157F, D222Y
  • 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-DQA1*01:03/DQB1*03:03 and peptides affected by the mutations

Weaker binding was found for 3 epitopes, while stronger binding was found for 12 entries. There is no tight binders for the HLA-DQA1*01:03/DQB1*03:03 in the reference immunopeptidome (IC50 affinity ≤ 50 nM). To avoid possible divisions by zero, we used + 1 regularization term in denominators when calculating percentages.

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HLA-DQA1*01:03/DQB1*03:03

Spike protein

G339H

Reference  QTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVAD
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Mutated    QTSNFRVQPTESIVRFPNITNLCPFHEVFNATTFASVYAWNRKRISNCVAD

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DQA1*01:03/DQB1*03:03 PFGEVFNATRFASVYA PFHEVFNATTFASVYA 596 265
HLA-DQA1*01:03/DQB1*03:03 FGEVFNATRFASVYA FHEVFNATTFASVYA 487 226
HLA-DQA1*01:03/DQB1*03:03 CPFGEVFNATRFASVYA CPFHEVFNATTFASVYA 672 312
HLA-DQA1*01:03/DQB1*03:03 CPFGEVFNATRFASVY CPFHEVFNATTFASVY 691 332
HLA-DQA1*01:03/DQB1*03:03 PFGEVFNATRFASVY PFHEVFNATTFASVY 597 288
HLA-DQA1*01:03/DQB1*03:03 LCPFGEVFNATRFASVY LCPFHEVFNATTFASVY 823 403

R346T

Reference  QPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNS
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Mutated    QPTESIVRFPNITNLCPFHEVFNATTFASVYAWNRKRISNCVADYSVIYNF

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DQA1*01:03/DQB1*03:03 PFGEVFNATRFASVYA PFHEVFNATTFASVYA 596 265
HLA-DQA1*01:03/DQB1*03:03 FGEVFNATRFASVYA FHEVFNATTFASVYA 487 226
HLA-DQA1*01:03/DQB1*03:03 CPFGEVFNATRFASVYA CPFHEVFNATTFASVYA 672 312
HLA-DQA1*01:03/DQB1*03:03 CPFGEVFNATRFASVY CPFHEVFNATTFASVY 691 332
HLA-DQA1*01:03/DQB1*03:03 PFGEVFNATRFASVY PFHEVFNATTFASVY 597 288
HLA-DQA1*01:03/DQB1*03:03 LCPFGEVFNATRFASVY LCPFHEVFNATTFASVY 823 403

N969K

Reference  ALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQID
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Mutated    ALGKLQDVVNHNAQALNTLVKQLSSKFGAISSVLNDILSRLDKVEAEVQID

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DQA1*01:03/DQB1*03:03 VKQLSSNFGAISSVL VKQLSSKFGAISSVL 476 1008

NS8 protein

G8stop

Reference  MKFLVFLGIITTVAAFHQECSLQSCTQHQPYVVDDPCPIHFYSKWYIRVGARKSAPLIELCVDEAGSKSPIQYIDIGNYTVSCLPFTINCQEPKLGSLVVRCSFYEDFLEYHDVRVVLDFI
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Mutated    MKFLVFL‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-DQA1*01:03/DQB1*03:03 VFLGIITTVAAFHQE VFL 429 -
HLA-DQA1*01:03/DQB1*03:03 LVFLGIITTVAAFHQ LVFL 494 -