In Silico Risk Assessment of HLA-A*02:06-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Caused by Cold Medicine Ingredients
Table 2
Binding affinities of the ingredients of cold medicines to the antigenic-peptide binding groove of HLA-A*02:06. Composite risk index is calculated by multiplying the maximum daily dose and the absolute value of GBVI/WSA_dG.
Drug name
Maximum dose/day (mmol)
GBVI_dG* (site N) (kcal/mol)
GBVI_dG* (site C) (kcal/mol)
Composite risk index (site N)**
Composite risk index (site C)**
Preferential binding site
Ethenzamide
6.356
−4.966
−5.335
31.565
33.914
C
Acetaminophen
5.954
−4.623
−4.608
27.523
27.438
N
Tranexamic acid
4.771
−5.550
−5.613
26.478
26.776
C
Ibuprofen
2.181
−5.491
−5.720
11.979
12.477
C
Abacavir***
1.789
−6.562
11.740
C
Guaifenesin
1.211
−6.482
−5.820
7.848
7.047
N
Guaiacolsulfonate
0.991
−4.562
−5.482
4.519
5.430
C
Pseudoephedrine
0.669
−5.581
−5.348
3.736
3.579
N
Caffeine
0.463
−5.333
−5.128
2.471
2.377
N
Loxoprofen
0.168
−6.468
−6.184
1.086
1.038
N
Dextromethorphan
0.130
−6.537
−6.315
0.847
0.819
N
Noscapine
0.116
−7.464
−6.792
0.867
0.789
N
d-Methylephedrine
0.139
−6.029
−5.636
0.838
0.784
N
Ambroxol
0.109
−6.763
−6.247
0.734
0.678
N
Dihydrocodeine
0.060
−5.401
−5.709
0.325
0.343
C
Bromhexine
0.029
−6.602
−5.655
0.192
0.164
N
Carbinoxamine
0.018
−7.616
−6.073
0.140
0.112
N
Isopropamide
0.012
−7.729
−6.102
0.097
0.076
N
d-Chlorpheniramine
0.010
−7.265
−6.690
0.070
0.064
N
Mequitazine
0.012
−7.021
−5.021
0.087
0.062
N
Clemastine
0.003
−7.680
−6.265
0.022
0.018
N
GBVI_dG: GBVI/WSA_dG. **Composite risk index: × (maximum daily dose). Binding to the HLA-B*57:01 molecule.