Summary

This strain contains 23 protein-level mutations:

  • 8 mutations in Spike protein: T95I, G142D, E154K, L452R, E484Q, D614G, P681R, Q1071H
  • 2 mutations in N protein: R203M, D377Y
  • 1 mutation in M protein: I82S
  • 1 mutation in NS3 protein: S26L
  • 1 mutation in NS7a protein: V82A
  • 2 mutations in NS9c protein: G50W, C68Y
  • 1 mutation in NSP3 protein: T749I
  • 1 mutation in NSP6 protein: T77A
  • 1 mutation in NSP12 protein: P323L
  • 2 mutations in NSP13 protein: G206C, M429I
  • 3 mutations in NSP15 protein: P65S, K259R, S261A

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*03:02 and peptides affected by the mutations

Weaker binding was found for 6 epitopes, while stronger binding was found for 8 entries. There are 132 tight binders for the HLA-A*03:02 in the reference immunopeptidome (IC50 affinity ≤ 50 nM); 0 of them became non-tight binders (0.0%) and 1 novel tight binder appeared (0.8%). To avoid possible divisions by zero, we used + 1 regularization term in denominators when calculating percentages.

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HLA-A*03:02

Spike protein

G142D

Reference  LLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCT
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Mutated    LLIVNNATNVVIKVCEFQFCNDPFLDVYYHKNNKSWMKSEFRVYSSANNCT

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*03:02 GVYYHKNNK DVYYHKNNK 119 3887

E154K

Reference  KVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDL
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Mutated    KVCEFQFCNDPFLDVYYHKNNKSWMKSEFRVYSSANNCTFEYVSQPFLMDL

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*03:02 KSWMESEFR KSWMKSEFR 465 224

L452R

Reference  DDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGS
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Mutated    DDFTGCVIAWNSNNLDSKVGGNYNYRYRLFRKSNLKPFERDISTEIYQAGS

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*03:02 YLYRLFRK YRYRLFRK 327 22983
HLA-A*03:02 KVGGNYNYL KVGGNYNYR 12848 234
HLA-A*03:02 LYRLFRKSNLK RYRLFRKSNLK 242 72

Q1071H

Reference  GYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFV
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Mutated    GYHLMSFPQSAPHGVVFLHVTYVPAHEKNFTTAPAICHDGKAHFPREGVFV

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*03:02 VTYVPAQEK VTYVPAHEK 65 31
HLA-A*03:02 FLHVTYVPAQEK FLHVTYVPAHEK 819 401

N protein

R203M

Reference  GGSQASSRSSSRSRNSSRNSTPGSSRGTSPARMAGNGGDAALALLLLDRLN
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Mutated    GGSQASSRSSSRSRNSSRNSTPGSSMGTSPARMAGNGGDAALALLLLDRLN

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*03:02 SSRGTSPAR SSMGTSPAR 2510 340

NS7a protein

V82A

Reference  TCFSTQFAFACPDGVKHVYQLRARSVSPKLFIRQEEVQELYSPIFLIVAAI
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Mutated    TCFSTQFAFACPDGVKHVYQLRARSASPKLFIRQEEVQELYSPIFLIVAAI

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*03:02 SVSPKLFIR SASPKLFIR 308 1994

NSP6 protein

T77A

Reference  MSAFAMMFVKHKHAFLCLFLLPSLATVAYFNMVYMPASWVMRIMTWLDMVD
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Mutated    MSAFAMMFVKHKHAFLCLFLLPSLAAVAYFNMVYMPASWVMRIMTWLDMVD

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*03:02 TVAYFNMVY AVAYFNMVY 578 252

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*03:02 PTSFGPLVRK LTSFGPLVRK 868 88

NSP15 protein

K259R

Reference  HIVYGDFSHSQLGGLHLLIGLAKRFKESPFELEDFIPMDSTVKNYFITDAQ
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Mutated    HIVYGDFSHSQLGGLHLLIGLAKRFREAPFELEDFIPMDSTVKNYFITDAQ

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Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-A*03:02 LLIGLAKRFK LLIGLAKRFR 130 1918
HLA-A*03:02 HLLIGLAKRFK HLLIGLAKRFR 409 4359
HLA-A*03:02 LIGLAKRFK LIGLAKRFR 399 3992