Summary

This strain contains 25 protein-level mutations:

  • 7 mutations in Spike protein: EFR 156-158 deletion, E484K, S494P, D614G, E780A, D839V, T1027I
  • 3 mutations in N protein: A12S, 203-204 RG->KR, G212C
  • 1 mutation in M protein: I82T
  • 2 mutations in NS3 protein: S171L, V201F
  • 1 mutation in NS9b protein: M8I
  • 1 mutation in NS9c protein: G50N
  • 1 mutation in NSP2 protein: N269D
  • 3 mutations in NSP3 protein: M84V, R1297I, S1375Y
  • 1 mutation in NSP6 protein: V84F
  • 1 mutation in NSP10 protein: T111I
  • 2 mutations in NSP12 protein: S229N, P323L
  • 2 mutations in NSP13 protein: P77L, L455M

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*58:01 and peptides affected by the mutations

Weaker binding was found for 17 epitopes, while stronger binding was found for 13 entries. There are 150 tight binders for the HLA-B*58:01 in the reference immunopeptidome (IC50 affinity ≤ 50 nM); 0 of them became non-tight binders (0.0%) and 1 novel tight binder appeared (0.7%). To avoid possible divisions by zero, we used + 1 regularization term in denominators when calculating percentages.

Download figure  Export data to csv 
HLA-B*58:01

Spike protein

EFR 156-158 deletion

Reference  CEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQ
           |||||||||||||||||||||||||   |||||||||||||||||||||||||
Mutated    CEFQFCNDPFLGVYYHKNNKSWMES‑‑‑VYSSANNCTFEYVSQPFLMDLEGKQ

Export table to csv 
Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-B*58:01 RVYSSANNCTF - 126 -
HLA-B*58:01 KSWMESEFRV KSWMESV 187 -
HLA-B*58:01 MESEFRVYSSANNCTF MESVYSSANNCTF - 267
HLA-B*58:01 KSWMESEF KSWMES 465 -
HLA-B*58:01 KSWMESEFRVY KSWMESVY 167 832

T1027I

Reference  QSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSF
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    QSLQTYVTQQLIRAAEIRASANLAAIKMSECVLGQSKRVDFCGKGYHLMSF

Export table to csv 
Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-B*58:01 RASANLAAT RASANLAAI 5883 333

M protein

I82T

Reference  LWPVTLACFVLAAVYRINWITGGIAIAMACLVGLMWLSYFIASFRLFARTR
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    LWPVTLACFVLAAVYRINWITGGIATAMACLVGLMWLSYFIASFRLFARTR

Export table to csv 
Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-B*58:01 IAMACLVGL TAMACLVGL 423 1182
HLA-B*58:01 IAMACLVGLM TAMACLVGLM 479 1090
HLA-B*58:01 IAMACLVGLMW TAMACLVGLMW 19 39

NS3 protein

S171L

Reference  FLCWHTNCYDYCIPYNSVTSSIVITSGDGTTSPISEHDYQIGGYTEKWESG
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    FLCWHTNCYDYCIPYNSVTSSIVITLGDGTTSPISEHDYQIGGYTEKWESG

Export table to csv 
Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-B*58:01 VTSSIVITS VTSSIVITL 2482 96

NS9c protein

G50N

Reference  AAVKPLLVPHHVVATVQEIQLQAAVGELLLLEWLAMAVMLLLLCCCLTD
           ||||||||||||||||||||||||| |||||||||||||||||||||||
Mutated    AAVKPLLVPHHVVATVQEIQLQAAVNELLLLEWLAMAVMLLLLCCCLTD

Export table to csv 
Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-B*58:01 VGELLLLEW VNELLLLEW 330 1071
HLA-B*58:01 AVGELLLLEW AVNELLLLEW 196 87

NSP3 protein

M84V

Reference  DAVIKTLQPVSELLTPLGIDLDEWSMATYYLFDESGEFKLASHMYCSFYPP
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    DAVIKTLQPVSELLTPLGIDLDEWSVATYYLFDESGEFKLASHMYCSFYPP

Export table to csv 
Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-B*58:01 EWSMATYYLF EWSVATYYLF 157 467
HLA-B*58:01 IDLDEWSMATYYLF IDLDEWSVATYYLF 380 1116
HLA-B*58:01 SMATYYLF SVATYYLF 493 1427
HLA-B*58:01 WSMATYYLFD WSVATYYLFD 490 1374
HLA-B*58:01 LDEWSMATYYLF LDEWSVATYYLF 65 180
HLA-B*58:01 WSMATYYLF WSVATYYLF 7 15

R1297I

Reference  VGHTDLMAAYVDNSSLTIKKPNELSRVLGLKTLATHGLAAVNSVPWDTIAN
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    VGHTDLMAAYVDNSSLTIKKPNELSIVLGLKTLATHGLAAVNSVPWDTIAN

Export table to csv 
Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-B*58:01 LSRVLGLKTL LSIVLGLKTL 1838 328

NSP6 protein

V84F

Reference  FVKHKHAFLCLFLLPSLATVAYFNMVYMPASWVMRIMTWLDMVDTSLSGFK
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    FVKHKHAFLCLFLLPSLATVAYFNMFYMPASWVMRIMTWLDMVDTSLSGFK

Export table to csv 
Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-B*58:01 LATVAYFNMV LATVAYFNMF 3556 279
HLA-B*58:01 ATVAYFNMV ATVAYFNMF 5612 474
HLA-B*58:01 MVYMPASWVM MFYMPASWVM 229 2515
HLA-B*58:01 MVYMPASW MFYMPASW 112 464
HLA-B*58:01 VAYFNMVYM VAYFNMFYM 878 222
HLA-B*58:01 NMVYMPASW NMFYMPASW 167 70
HLA-B*58:01 YFNMVYMPASW YFNMFYMPASW 507 249

NSP10 protein

T111I

Reference  PKGFCDLKGKYVQIPTTCANDPVGFTLKNTVCTVCGMWKGYGCSCDQLREP
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    PKGFCDLKGKYVQIPTTCANDPVGFILKNTVCTVCGMWKGYGCSCDQLREP

Export table to csv 
Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-B*58:01 FTLKNTVCTVCGMW FILKNTVCTVCGMW 345 5931

NSP12 protein

P323L

Reference  CVNCLDDRCILHCANFNVLFSTVFPPTSFGPLVRKIFVDGVPFVVSTGYHF
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    CVNCLDDRCILHCANFNVLFSTVFPLTSFGPLVRKIFVDGVPFVVSTGYHF

Export table to csv 
Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-B*58:01 FSTVFPPTSF FSTVFPLTSF 88 33

NSP13 protein

P77L

Reference  APGCDVTDVTQLYLGGMSYYCKSHKPPISFPLCANGQVFGLYKNTCVGSDN
           ||||||||||||||||||||||||| |||||||||||||||||||||||||
Mutated    APGCDVTDVTQLYLGGMSYYCKSHKLPISFPLCANGQVFGLYKNTCVGSDN

Export table to csv 
Allele Reference peptide Mutated peptide Reference affinity (IC50, nM) Mutated affinity (IC50, nM)
HLA-B*58:01 MSYYCKSHKP MSYYCKSHKL 3227 360
HLA-B*58:01 KSHKPPISFPL KSHKLPISFPL 716 187