TABLE 2.
Molecular docking study between selected ligands and SARS-CoV-2 Mpro. Intermolecular docking values, presented with their interaction energy (∆E binding), H-bond residues, interacting residues are shown and Ligand efficiency calculation for SARS-CoV-2 Mpro complexes.
| Compound | Docking results | Ligand Efficiency | |||
|---|---|---|---|---|---|
| ∆E binding (kcal mol−1) a | H-bonds b | Residue interactions b | K d | LE (kcal mol−1) | |
| 13b c | –7.2 | Leu167; Glu166 | Arg188; Asn142; Asp187; Cys145; Gln189; Glu166; Gly143; His164; His163; His41; Leu167; Leu27; Met165; Met49; Phe140; Pro168; Ser144; Thr25; Thr26 | 5.29 × 10–6 | 0.167 |
| CTR6 | –7.1 | Met49; Gln189; Glu166; Gln192 | Arg188; Asn142; Cys145; Gln189; Gln192; Glu166; Gly143; His41; Leu167; Met49; Pro168; Thr190; Thr25 | 6.26 × 10–6 | 0.253 |
| 7HC6 | –6.7 | Glu166; Ser46 | Arg188; Cys145; Cys44; Gln189; Gln192; Glu166; His41; Met165; Met49; Ser46; Thr25; Thr45 | 12.3 × 10–6 | 0.304 |
| 7HC5 | –6.6 | – | Cys145; Glu166; His164; His163; His41; Met165; Met49; Phe140; Ser144; Ser305 | 14.6 × 10–6 | 0.347 |
| CTR9 | –6.6 | Met165; Asn142 | Asn142; Cys145; Cys44; Glu166; Gly143; His164; His163; Leu141; Met165; Met49; Phe140; Ser144; Ser46; Thr25; Thr45 | 14.6 × 10–6 | 0.300 |
| 7HC3 | –6.6 | – | Cys145; Glu166; His164; His163; His41; Leu141; Met165; Met49; Phe140; Ser144; Ser305 | 14.6 × 10–6 | 0.347 |
| 8HQ6 | –6.5 | – | Cys145; Cys44; Glu166; His164; His41; Leu141; Met165; Met49; Phe140; Ser144; Ser305; Thr25 | 17.2 × 10–6 | 0.309 |
| CTR4 | –6.5 | His163; Glu166; Met49 | Asn142; Cys145; Cys44; Glu166; His163; His172; Leu141; Met165; Met49; Phe140; Ser144; Ser305; Ser46; Thr25; Thr45 | 17.2 × 10–6 | 0.240 |
| CTR5 | –6.4 | His163; Thr26; Gly143; Thr25 | Asn142; Cys145; Glu166; Gly143; His163; Leu141; Met165; Phe140; Ser144; Thr24; Thr25; Thr26 | 20.4 × 10–6 | 0.278 |
| CTR1 | –6.3 | His41; Glu166; Arg188; Leu27; Thr25 | Arg188; Asn142; Cys145; Gln189; Gln192; Glu166; Gly143; His41; Leu27; Met165; Met49; Thr190; Thr25; Thr26 | 24.1 × 10–6 | 0.273 |
| CTR3 | –6.3 | Glu166; His163; Asn142 | Asn142; Cys145; Cys44; Glu166; His163; His172; Leu141; Met165; Met49; Phe140; Ser144; Ser305; Ser46; Thr25; Thr45 | 24.1 × 10–6 | 0.262 |
| 8HQ5 | –6.3 | Gln189 | Cys145; Gln189; Glu166; His163; Met165; Met49; Phe140; Ser144; Ser305 | 24.1 × 10–6 | 0.350 |
| 8HQ7 | –6.2 | – | Cys145; Gln189; Glu166; His163; Met165; Met49; Phe140; Ser144; Ser305 | 28.6 × 10–6 | 0.344 |
| 78HC2 | –6.1 | His163 | Asn142; Cys145; Gln189; Glu166; His163; Met165; Phe140; Ser144 | 33.8 × 10–6 | 0.358 |
| CTR7 | –6.1 | Thr25; Cys44 | Arg188; Cys44; Gln189; Gln192; Glu166; His41; Leu167; Met165; Met49; Pro168; Ser46; Thr190; Thr25; Thr45 | 33.8 × 10–6 | 0.234 |
| CTR2 | –6.1 | Leu141; Thr25; His163; Asn142 | Asn142; Cys145; Glu166; Gly143; His163; Leu141; Leu27; Met165; Met49; Phe140; Ser144; Ser46; Thr25 | 33.8 × 10–6 | 0.203 |
| CTR8 | –6.0 | Gly143 | Asn142; Cys145; Glu166; Gly143; His163; Leu141; Met165; Phe140; Ser144; Thr25; Thr26 | 40.1 × 10–6 | 0.285 |
| 78HC1 | –5.7 | – | Cys145; Glu166; His163; Leu141; Met165; Phe140; Ser144; Ser305 | 66.5 × 10–6 | 0.380 |
| 7HC2 | –5.7 | – | Cys145; Glu166; His164; His163; Leu141; Met165; Phe140; Ser144; Ser305 | 66.5 × 10–6 | 0.356 |
| 7HC4 | –5.7 | Phe140; Asn142 | Asn142; Cys145; Glu166; Gly143; His163; His41; Leu141; Leu27; Met165; Phe140; Ser144 | 66.5 × 10–6 | 0.335 |
| 7HC1 | –5.6 | – | Cys145; Glu166; His164; His163; His41; Met165; Phe140; Ser144; Ser305 | 78.6 × 10–6 | 0.373 |
| 8HQ4 | –5.6 | Glu166 | Arg188; Cys145; Gln189; Glu166; His163; Leu141; Met165; Met49; Phe140; Ser144; Ser305 | 78.7 × 10–6 | 0.350 |
| 7HC7 | –5.5 | His163; Phe140 | Cys145; Glu166; His163; Leu141; Met165; Phe140; Ser144 | 93.2 × 10–6 | 0.392 |
| 8HQ8 | –5.4 | Met165 | Asn142; Cys145; Glu166; His41; Met165; Met49 | 110 × 10–6 | 0.337 |
| 8HQ2 | –5.3 | Glu166 | Cys145; Glu166; His163; Met165; Phe140; Ser144; Ser305 | 130 × 10–6 | 0.378 |
| 8HQ3 | –5.3 | Glu166 | Cys145; Gln189; Glu166; His163; Met165; Met49; Phe140; Ser144; Ser305 | 130 × 10–6 | 0.353 |
| 8HQ1 | –5.1 | – | Asn142; Glu166; His164; His163; Leu141; Met165; Phe140; Ser144; Ser305 | 182 × 10–6 | 0.392 |
a
In each site, the energy was calculated to see which site had the highest degree of union with the ligand.
b
The reason of 3 Å was the length of the Hydrogen bond ranges from 2.6 Å to 3.1 Å based on observations from the PDB.
c
The ligand 13b is our reference ligand and was obtained from PDB (id: 6Y2E).
His41 and Cys145 residues of the catalytic site are highlighted with bold font.