Table 4.
Molecular binding interactions of the selected drugs with human ACE2, BTK and TMPRSS2.
| Ligand | Binding Energy (kcal/mol) | No. of HBs | Interacting Residues with HBs | HB Distance (Å) |
|---|---|---|---|---|
| ACE2 | ||||
| Acalabrutinib | −9.4 | 2 | GLN98, TYR196 | 3.27, 2.85 |
| Dasatinib | −8.9 | 4 | ALA348, ASP382, TYR385 | 2.98, 2.95, 3.01, 3.06 |
| Evobrutinib | −8.9 | 1 | TYR385 | 2.81 |
| Fostamatinib | −8.6 | 2 | ASN210, GLU208 | 2.74, 3.14 |
| Ibrutinib | −9.4 | 0 | NA | NA |
| Inositol | −6.2 | 6 | GLU208, GLN98, GLN102, TYR202, TYR196 | 2.70, 2.90, 2.77, 2.71, 2.89, 2.95 |
| Spebrutinib | −8.2 | 3 | ASP382, HSD401, TYR385 | 2.81, 3.71, 3.12 |
| XL418 | −9.2 | 2 | SER43, ASP382 | 2.80, 3.24 |
| Zanubrutinib * | −9.8 | 2 | GLY205, TYR202 | 3.20, 2.81 |
| BTK | ||||
| Acalabrutinib | −7.3 | 0 | NA | NA |
| Dasatinib | −6.9 | 4 | ASP107, ASN161, LYS160 | 3.04, 3.03, 3.04, 2.91 |
| Evobrutinib | −7.3 | 3 | GLU45, PHE44, TYR42 | 3.30, 3.03, 3.15 |
| Fostamatinib | −6.8 | 2 | ASN170 | 2.88, 3.09 |
| Ibrutinib * | −7.4 | 2 | VAL34 | 2.72, 3.12 |
| Inositol | −5.0 | 4 | SER86, GLU90, GLU96 | 2.94, 2.96, 2.84, 3.14 |
| Spebrutinib | −6.7 | 2 | GLU45, TYR42 | 3.20, 3.28 |
| XL418 | −7.0 | 0 | LYS71 | 2.70 |
| Zanubrutinib | −7.6 | 0 | NA | NA |
| TMPRSS2 | ||||
| Acalabrutinib | −7.4 | 1 | ASN303 | 3.12 |
| Dasatinib | −8.1 | 5 | GLU385, ASP440, GLY383, CYS465, ASN433 | 3.06, 3.15, 2.97, 3.31, 3.03 |
| Evobrutinib | −7.4 | 3 | SER441, SER436, GLY462 | 3.00, 3.24, 3.02 |
| Fostamatinib | −8.1 | 5 | GLY464, GLY439, SER460, VAL280, HSD296 | 3.15, 3.26, 3.03, 2.88, 3.09 |
| Ibrutinib | −7.6 | 1 | ASN192 | 3.10 |
| Inositol | −5.4 | 10 | LEU378, GLY377, ASN451, GLN253, ASP144, SER448, ASN450 | 2.81, 3.12, 2.92, 2.89, 2.92, 2.98, 3.16, 3.07, 2.94, 3.14 |
| Spebrutinib | −6.5 | 1 | ASN192 | 3.03 |
| XL418 | −7.6 | 3 | PHE156, ASN451, CYS241 | 3.26, 3.15, 2.80 |
| Zanubrutinib * | −8.2 | 1 | THR287 | 3.21 |
* indicates the complex selected for further studies; ACE2—angiotensin-converting enzyme 2; BTK—Bruton’s tyrosine kinase; HBs—hydrogen bonds; NA—not available; TMPRSS2—transmembrane serine protease 2.