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*06:01/DQB1*03:03 and peptides affected by the mutations

Weaker binding was found for 4 epitopes, while stronger binding was found for 49 entries. There is no tight binders for the HLA-DQA1*06:01/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*06:01/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*06:01/DQB1*03:03 FGEVFNATRFASVYA FHEVFNATTFASVYA 866 192
HLA-DQA1*06:01/DQB1*03:03 CPFGEVFNATRFASVYA CPFHEVFNATTFASVYA 1190 291
HLA-DQA1*06:01/DQB1*03:03 PFGEVFNATRFASVY PFHEVFNATTFASVY 1001 246
HLA-DQA1*06:01/DQB1*03:03 PFGEVFNATRFASVYA PFHEVFNATTFASVYA 861 219
HLA-DQA1*06:01/DQB1*03:03 CPFGEVFNATRFASVY CPFHEVFNATTFASVY 1033 281
HLA-DQA1*06:01/DQB1*03:03 CPFGEVFNATRFASV CPFHEVFNATTFASV 1323 369
HLA-DQA1*06:01/DQB1*03:03 LCPFGEVFNATRFASVY LCPFHEVFNATTFASVY 1368 389
HLA-DQA1*06:01/DQB1*03:03 LCPFGEVFNATRFASVYA LCPFHEVFNATTFASVYA 1565 465
HLA-DQA1*06:01/DQB1*03:03 NLCPFGEVFNATRFASVYA NLCPFHEVFNATTFASVYA 1217 405
HLA-DQA1*06:01/DQB1*03:03 PFGEVFNATRFASVYAW PFHEVFNATTFASVYAW 782 264
HLA-DQA1*06:01/DQB1*03:03 LCPFGEVFNATRFASV LCPFHEVFNATTFASV 1265 430
HLA-DQA1*06:01/DQB1*03:03 TNLCPFGEVFNATRFASVYA TNLCPFHEVFNATTFASVYA 1168 403
HLA-DQA1*06:01/DQB1*03:03 GEVFNATRFASVYAW HEVFNATTFASVYAW 598 209
HLA-DQA1*06:01/DQB1*03:03 FGEVFNATRFASVYAW FHEVFNATTFASVYAW 569 204
HLA-DQA1*06:01/DQB1*03:03 FGEVFNATRFASVYAWN FHEVFNATTFASVYAWN 707 264
HLA-DQA1*06:01/DQB1*03:03 CPFGEVFNATRFASVYAW CPFHEVFNATTFASVYAW 1130 436
HLA-DQA1*06:01/DQB1*03:03 PFGEVFNATRFASVYAWN PFHEVFNATTFASVYAWN 1036 425
HLA-DQA1*06:01/DQB1*03:03 GEVFNATRFASVYAWN HEVFNATTFASVYAWN 533 225
HLA-DQA1*06:01/DQB1*03:03 LCPFGEVFNATRFASVYAW LCPFHEVFNATTFASVYAW 863 374
HLA-DQA1*06:01/DQB1*03:03 NLCPFGEVFNATRFASVYAW NLCPFHEVFNATTFASVYAW 855 371
HLA-DQA1*06:01/DQB1*03:03 LCPFGEVFNATRFASVYAWN LCPFHEVFNATTFASVYAWN 807 361
HLA-DQA1*06:01/DQB1*03:03 CPFGEVFNATRFASVYAWN CPFHEVFNATTFASVYAWN 793 369
HLA-DQA1*06:01/DQB1*03:03 FGEVFNATRFASVYAWNR FHEVFNATTFASVYAWNR 861 405
HLA-DQA1*06:01/DQB1*03:03 GEVFNATRFASVYAWNR HEVFNATTFASVYAWNR 580 283

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*06:01/DQB1*03:03 FGEVFNATRFASVYA FHEVFNATTFASVYA 866 192
HLA-DQA1*06:01/DQB1*03:03 CPFGEVFNATRFASVYA CPFHEVFNATTFASVYA 1190 291
HLA-DQA1*06:01/DQB1*03:03 PFGEVFNATRFASVY PFHEVFNATTFASVY 1001 246
HLA-DQA1*06:01/DQB1*03:03 PFGEVFNATRFASVYA PFHEVFNATTFASVYA 861 219
HLA-DQA1*06:01/DQB1*03:03 CPFGEVFNATRFASVY CPFHEVFNATTFASVY 1033 281
HLA-DQA1*06:01/DQB1*03:03 CPFGEVFNATRFASV CPFHEVFNATTFASV 1323 369
HLA-DQA1*06:01/DQB1*03:03 LCPFGEVFNATRFASVY LCPFHEVFNATTFASVY 1368 389
HLA-DQA1*06:01/DQB1*03:03 LCPFGEVFNATRFASVYA LCPFHEVFNATTFASVYA 1565 465
HLA-DQA1*06:01/DQB1*03:03 NLCPFGEVFNATRFASVYA NLCPFHEVFNATTFASVYA 1217 405
HLA-DQA1*06:01/DQB1*03:03 PFGEVFNATRFASVYAW PFHEVFNATTFASVYAW 782 264
HLA-DQA1*06:01/DQB1*03:03 LCPFGEVFNATRFASV LCPFHEVFNATTFASV 1265 430
HLA-DQA1*06:01/DQB1*03:03 TNLCPFGEVFNATRFASVYA TNLCPFHEVFNATTFASVYA 1168 403
HLA-DQA1*06:01/DQB1*03:03 GEVFNATRFASVYAW HEVFNATTFASVYAW 598 209
HLA-DQA1*06:01/DQB1*03:03 FGEVFNATRFASVYAW FHEVFNATTFASVYAW 569 204
HLA-DQA1*06:01/DQB1*03:03 FGEVFNATRFASVYAWN FHEVFNATTFASVYAWN 707 264
HLA-DQA1*06:01/DQB1*03:03 CPFGEVFNATRFASVYAW CPFHEVFNATTFASVYAW 1130 436
HLA-DQA1*06:01/DQB1*03:03 PFGEVFNATRFASVYAWN PFHEVFNATTFASVYAWN 1036 425
HLA-DQA1*06:01/DQB1*03:03 GEVFNATRFASVYAWN HEVFNATTFASVYAWN 533 225
HLA-DQA1*06:01/DQB1*03:03 LCPFGEVFNATRFASVYAW LCPFHEVFNATTFASVYAW 863 374
HLA-DQA1*06:01/DQB1*03:03 NLCPFGEVFNATRFASVYAW NLCPFHEVFNATTFASVYAW 855 371
HLA-DQA1*06:01/DQB1*03:03 LCPFGEVFNATRFASVYAWN LCPFHEVFNATTFASVYAWN 807 361
HLA-DQA1*06:01/DQB1*03:03 EVFNATRFASVYAWN EVFNATTFASVYAWN 537 246
HLA-DQA1*06:01/DQB1*03:03 CPFGEVFNATRFASVYAWN CPFHEVFNATTFASVYAWN 793 369
HLA-DQA1*06:01/DQB1*03:03 FGEVFNATRFASVYAWNR FHEVFNATTFASVYAWNR 861 405
HLA-DQA1*06:01/DQB1*03:03 GEVFNATRFASVYAWNR HEVFNATTFASVYAWNR 580 283

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*06:01/DQB1*03:03 VFLGIITTVAAFHQE VFL 383 -
HLA-DQA1*06:01/DQB1*03:03 LVFLGIITTVAAFHQ LVFL 407 -
HLA-DQA1*06:01/DQB1*03:03 LVFLGIITTVAAFHQE LVFL 480 -
HLA-DQA1*06:01/DQB1*03:03 FLGIITTVAAFHQEC FL 492 -