Table 2.
The binding affinities of the potential pyrimidonic pharmaceuticals with 3-chymotrypsin-like protease (3CLpro).
| Pharmaceutical Name | Binding Percentage a | Score ± SD (kcal/mol) b |
RMSD | Hydrogen Bond (Number of Bonds/Number of Conformations) | Van Der Waals (Distance) (Number of Bonds/Number of Conformations) |
|---|---|---|---|---|---|
| Uracil mustard | a. 100 * c. 89 d. 100 e. 100 All. 100 |
a. −4.6 ± 0.14 c. −4.6 ± 0.14 d. −4.6 ± 0.14 e. −4.6 ± 0.14 |
a. 0.00–7.13 c. 0.00–7.13 d. 0.00–7.13 e. 0.00–7.13 |
a. HIS 163 (5/5), GLU 166 (3/3), LEU 141 (3/3), ASN 142 (1/1) | a. HIS 163 (31/5), GLU 166 (40/8), LEU 141 (19/5), ASN 142 (50/7), PHE 140 (8/5) c. MET 49 (52/7), HIS 164 (12/4) d. GLN 189 (32/9), MET 165 (28/8) e. HIS 41 (53/9), SER 144 (10/5), GLY 143 (4/1), CYS 145 (28/9) |
| Cytarabine | a. 67 c. 67 d. 67 e. 67 All. 67 |
a. −5.4 ± 0.26 c. −5.4 ± 0.26 d. −5.4 ± 0.26 e. −5.4 ± 0.26 |
a. 0.00–6.07 c. 0.00–6.07 d. 0.00–6.07 e. 0.00–6.07 |
a. GLU 166 (3/3), LEU 141 (2/2), HIS 163 (1/1), PHE 140 (2/2), ASN 142 (1/1) c. HIS 164 (2/2) d. GLN 189 (1/1) e. GLY 143 (1/1) |
a. GLU 166 (44/5), LEU 141 (18/3), HIS 163 (18/4), PHE 140 (19/3), ASN 142 (27/6) c. HIS 164 (10/4), MET 49 (20/6) d. MET 165 (28/4), GLN 189 (4/2) e. GLY 143 (11/2), SER 144 (8/2), CYS 145 (15/6), HIS 41 (21/5) |
| Floxuridine | a. 44 c. 44 d. 44 e. 44 All. 56 |
a. 5.5 ± 0.13 c. 5.6 ± 0.25 d. 5.6 ± 0.25 e. 5.6 ± 0.19 |
a. 3.24–8.28 c. 0.00–8.28 d. 0.00–8.28 e. 0.00–8.28 |
a. ASN 142 (1/1), HIS 163 (2/2), GLU 166 (2/2), PHE 140 (1/1), LEU 141 (1/1) e. HIS 41 (1/1) |
a. GLU 166 (23/4), LEU 141 (6/2), PHE 140 (8/2), HIS 163 (5/2), ASN 142 (19/4) c. MET 49 (9/2), HIS 164 (3/3) d. MET 165 (5/3), GLN 189 (4/1) e. GLY 143 (6/1), SER 144 (4/1), CYS 145 (5/3), HIS 41 (16/3) |
| Trifluridine | a. 44 c. 44 d. 44 e. 44 f. 11 All. 56 |
a. −6.03 ± 0.17 c. −6.03 ± 0.17 d. −6.03 ± 0.17 e. −6.03 ± 0.17 f. −5.7 |
a. 0.00–5.58 c. 0.00–5.58 d. 0.00–5.58 e. 0.00–5.58 f. 28.34–30.21 |
a. GLU 166 (2/2), ASN 142 (1/1). c. HIS 164 (2/2) e. GLY 143 (1/1) |
a. GLU 166 (18/4), ASN 142 (15/3), HIS 163 (2/1), LEU 141 (2/1) b. c. HIS 164 (10/3), MET 49 (17/4) d. MET 165 (19/4), GLN 189 (1/1). e. CYS 145 (13/4), GLY 143 (10/2), HIS 41 (10/4) f. SER 284 (9/1) |
| Stavudine | a. 44 c. 56 d. 44 e. 56 All. 56 |
a. −5.6 ± 0.28 c. −5.6 ± 0.28 d. −5.6 ± 0.28 e. −5.6 ± 0.28 |
a. 27.12–32.34 c. 27.12–35.03 d. 27.12–32.34 e. 27.12–35.03 |
a. GLU 166 (1/1) | a. ASN 142 (13/3), GLU 166 (14/4), HIS 163 (2/1), LEU 141 (1/1) c. HIS 164 (6/3), MET 49 (20/5) d. MET 165 (12/4), GLN 189 (1/1) e. HIS 41 (39/5), GLY 143 (9/2), CYS 145 (7/3) |
| Lamivudine | a. 56 c. 44 d. 44 e. 56 f. 11 All. 67 |
a. −5.4 ± 0.24 c. −5.4 ± 0.28 d. −5.4 ± 0.25 e. −5.4 ± 0.24 f. −5.2 |
a. 0.00–4.77 c. 0.00–3.38 d. 0.00–4.77 e. 0.00–4.77 f. 26.28–28.62 |
a. HIS 163 (3/3), ASN 142 (1/1), PHE 140 (3/3), LEU 141 (2/2), GLU 166 (2/2) d. GLN 189 (1/1) e. SER 144 (2/2) |
a. HIS 163 (26/5), ASN 142 (19/2), PHE 140 (31/5), LEU 141 (15/5), GLU 166 (46/5) c. MET 49 (12/4), HIS 164 (1/1) d. GLN 189 (12/2), MET 165 (10/4), LEU 167 (1/1) e. SER 144 (18/4), HIS 41 (5/2), CYS 145 (7/3) f. LEU 286 (1/1) |
| Zalcitabine | a. 44 b. 11 c. 33 d. 44 e. 44 f. 22 All. 67 |
a. −5.5 ± 0.29 b. −5.1 c. −5.4 ± 0.35 d. −5.5 ± 0.29 e. −5.5 ± 0.29 f. −5.1 ± 0.00 |
a. 0.00–6.39 b. 28.02–29.48 c. 0.00–6.39 d. 0.00–6.39 e. 0.00–6.39 f. 28.02–31.88 |
a. PHE 140 (3/3), LEU 141 (1/1), GLU 166 (3/3), ASN 142 (1/1) c. GLN 189 (1/1) |
a. HIS 163 (15/3), PHE 140 (16/3), LEU 141 (9/3), GLU 166 (25/4), ASN 142 (11/3) b. LYS 5 (6/1), ARG 4 (12/1), PHE 3 (4/1) c. MET 49 (16/2), HIS 164 (5/3) d. GLN 189 (6/2), MET 165 (15/4) e. SER 144 (7/2), HIS 41 (13/2), CYS 145 (6/3) f. SER 284 (4/1), LEU 286 (4/1) |
| Telbivudine | a. 56 c. 44 d. 44 e. 56 f. 11 All. 67 |
a. −5.6 ± 0.38 c. −5.7 ± 0.42 d. −5.7 ± 0.42 e. −5.6 ± 0.38 f. −5.3 |
a. 0.00–7.50 c. 0.00–7.50 d. 0.00–7.50 e. 0.00–7.50 f. 22.85–24.17 |
a. ASN 142 (2/1), HIS 163 (3/3), GLU 166 (1/1), PHE 140 (2/2), LEU 141 (1/1) c. HIS 164 (1/1) d. GLN 189 (1/1) e. HIS 41 (1/1) |
a. GLU 166 (36/4), HIS 163 (11/3), PHE 140 (11/3), ASN 142 (27/5), LEU 141 (9/3) c. HIS 164 (6/3), MET 49 (27/3) d. GLN 189 (10/3), MET 165 (14/4), e. CYS 145 (11/4), SER 144 (8/2), GLY 143 (3/1), HIS 41 (12/5) f. LEU 286 (5/1) |
| Tipiracil | a. 56 b. 11 c. 44 d. 44 e. 44 f. 11 All. 67 |
a. −5.8 ± 0.16 b. −5.7 c. −5.9 ± 0.17 d. −5.8 ± 0.08 e. −5.9 ± 0.17 f. −5.7 |
a. 26.28–29.69 b. 19.12–20.08 c. 26.28–29.69 d. 26.67–29.69 e. 26.28–29.69 f. 19.12–20.08 |
a. HIS 163 (2/2), GLU 166 (2/1), PHE 140 (2/2), ASN 142 (1/1) b. LYS 5 (1/1) c. HIS 164 (1/1) e. GLY 143 (1/1) |
a. HIS 163 (14/3), GLU 166 (40/4), PHE 140 (8/3), ASN 142 (22/4), LEU 141 (10/3) b. PHE 3 (6/1), LYS 5 (9/1), ARG 4 (5/1) c. HIS 164 (8/4), MET 49 (22/3) d. MET 165 (9/3), GLN 189 (13/3) e. GLY 143 (7/2), HIS 41 (26/4), SER 144(2/1), CYS 145 (13/4) f. SER 284 (7/1), LEU 286 (2/1) |
| Citicoline | a. 56 * c. 56 d. 56 e. 56 All. 56 |
a. −7.0 ± 0.19 c. −7.0 ± 0.19 d. −7.0 ± 0.19 e. −7.0 ± 0.19 |
a. 0.00–8.01 c. 0.00–8.01 d. 0.00–8.01 e. 0.00–8.01 |
a. PHE 140 (2/2), GLU 166 (4/4), HIS 163 (3/3), ASN 142 (2/1), LEU 141 (1/1) e. SER 144 (1/1) |
a. PHE 140 (24/5), GLU 166 (57/5), HIS 163 (21/5), ASN 142 (34/5), LEU 141 (21/5) c. MET 49 (23/5), HIS 164 (1/1) d. MET 165 (29/5), GLN 189 (6/3) e. SER 144 (12/3), GLY 143 (4/1), CYS 145 (9/5), HIS 41 (21/5) |
| Uridine triacetate | a. 56 c. 56 d. 56 e. 56 f. 11 All. 67 |
a. −6.2 ± 0.26 c. −6.2 ± 0.26 d. −6.2 ± 0.26 e. −6.2 ± 0.26 f. −6.4 |
a. 0.00–6.79 c. 0.00–6.79 d. 0.00–6.79 e. 0.00–6.79 f. 24.97–28.01 |
a. HIS 163 (2/2), GLU 166 (3/2) e. HIS 41 (1/1) |
a. HIS 163 (5/2), GLU 166 (31/5), ASN 142 (30/5), PHE 140 (4/2), LEU 141 (6/2) c. MET 49 (18/5), HIS 164 (5/2) d. GLN 189 (15/4), MET 165 (18/4) e. CYS 145 (16/5), HIS 41 (35/5), SER 144 (4/2), GLY 143 (2/1) f. LEU 286 (1/1) |
a Binding percentage was calculated based on the number of conformations attached to the active sites of the CLpro (nine conformations in total). b SD based on the other score energies of conformations. * Alphabetical order indicates the type of active site involved in bonding: a. S1 site, b. S1 site from the other promotor, c. S2 site, d. S4 site, e. S’1 site, and f. SER 284, ALA 285, and LEU 286 residues. When letters are missing, this means no interactions were observed at that site.