Table 3.
Molecular binding interactions of the selected drugs with nonstructural proteins (RdRp, Nsp14, Mpro and PLpro) of SARS-CoV-2.
| Ligand | Binding Energy (kcal/mol) | No. of HBs | Interacting Residues with HBs | HB Distance (Å) |
|---|---|---|---|---|
| RdRp | ||||
| Acalabrutinib | −8.3 | 1 | HSD133 | 2.78 |
| Dasatinib | −8.5 | 3 | TYR728, GLU58, ASP36 | 2.96, 3.21, 2.97 |
| Evobrutinib | −7.6 | 2 | THR760, SER772 | 3.17, 3.33 |
| Fostamatinib | −8.8 | 7 | THR129, ASN781, SER709, LYS47, HSD133 | 2.69, 2.62, 2.96, 2.82, 2.85, 3.10, 2.82 |
| Ibrutinib | −9.0 | 3 | GLU58, ARG55, ARG733 | 3.03, 3.17, 2.88 |
| Inositol | −6.9 | 10 | HSD133, SER789, LYS788, ALA706, ASN781, GLY774, TYR129, LYS47 | 2.70, 3.35, 3.16, 3.19, 2.79, 2.87, 2.96, 2.90, 2.74, 3.04 |
| Spebrutinib | −7.8 | 4 | TYR129, ASN138, LYS47, ASP711 | 3.19, 3.17, 3.07, 3.11 |
| XL418 | −8.6 | 1 | ASN781 | 3.27 |
| Zanubrutinib * | −9.1 | 2 | HSD133, SER709 | 2.90, 3.20 |
| NSP14 | ||||
| Acalabrutinib | −7.5 | 2 | ARG76, TRP247 | 3.21, 2.96 |
| Dasatinib | −8.1 | 6 | CYS414, GLY416, GLY417, ASP415, VAL287 | 3.24, 3.21, 2.80, 2.84, 3.07, 2.91 |
| Evobrutinib | −8.3 | 2 | ASP352, ARG400 | 2.79, 2.72 |
| Fostamatinib | −8.5 | 5 | ASP10, SER28, GLY17,THR5 | 2.76, 2.92, 2.97, 2.88, 3.19 |
| Ibrutinib * | −8.9 | 1 | PHE286 | 3.21 |
| Inositol | −5.8 | 6 | PHE73, MET62, GLN246, ILE74, ASP243 | 3.08, 3.22, 2.62, 2.81, 2.70, 3.13 |
| Spebrutinib | −7.4 | 2 | GLN145, GLU191 | 3.10, 3.25, 3.22 |
| XL418 | −10.5 | 0 | NA | NA |
| Zanubrutinib | −8.5 | 3 | GLY17, SER28, ASP10 | 2.80, 2.87, 3.18 |
| Mpro | ||||
| Acalabrutinib | −8.5 | 0 | NA | NA |
| Dasatinib | −7.5 | 1 | ASP245 | 2.82 |
| Evobrutinib | −7.6 | 4 | ARG40, GLY183, PRO184 | 3.03, 3.35, 3.17, 3.23 |
| Fostamatinib | −7.4 | 4 | THR111, GLN110 | 2.80, 3.14, 3.09, 2.80 |
| Ibrutinib * | −8.7 | 3 | THR292, LYS102 | 2.65, 2.86, 3.00 |
| Inositol | −6.3 | 14 | ASP289, LEU287, TYR239, THR199, ASN238, THR198, ASP238, ARG131 | 2.79, 3.07, 3.06, 3.00, 3.10, 2.95, 2.71, 3.18, 3.17, 2.95, 3.24, 2.91, 2.90, 3.17 |
| Spebrutinib | −6.9 | 0 | NA | NA |
| XL418 | −8.2 | 1 | GLN110 | 3.12 |
| Zanubrutinib | −8.1 | 0 | NA | NA |
| PLpro | ||||
| Acalabrutinib | −6.6 | 1 | MET206 | 2.85 |
| Dasatinib | −6.7 | 3 | ALA176, LEU178, PHE173 | 2.98, 3.14, 3.10 |
| Evobrutinib | −6.2 | 2 | GLU238, SER180 | 2.96, 3.15 |
| Fostamatinib | −6.2 | 2 | ASP164, GLY163 | 2.85, 3.35 |
| Ibrutinib | −7 | 1 | LYS157 | 3.22 |
| Inositol | −5.7 | 6 | ASN308, SER180, GLU124, LYS126, ASN172 | 2.96, 2.96, 3.04, 3.10, 3.14, 3.22 |
| Spebrutinib | −6.1 | 1 | ARG166 | 3.08 |
| XL418 | −6.9 | 2 | ASP179, GLN174 | 2.86, 3.29 |
| Zanubrutinib * | −7.3 | 3 | SER180, GLU238, ASN308 | 2.86, 3.05, 3.05 |
* indicates the complex selected for further studies; HBs—hydrogen bonds; Mpro—main protease; NA—not available; RdRp—RNA-dependent RNA polymerase; PLpro—papain-like cysteine protease.