Table 3.
Potential off-target effects for selected drugs according to sub-structural similarity of binding patterns from Drug ReposER application.
| Potential off-targets that may cause adverse effects | ||||
|---|---|---|---|---|
| Drug ID1 | Query PDBID of structure with known binding site | Hit PDB of structure with a potential alternate / off-target site (Docking score) | Macromolecule and its associated pathways or mechanisms for off-target sites / involvement in antiviral activity | Potential/reported outcomes associated with the off-target site |
| LOC | 5nm5B | 2gk1I (−7.5) | Beta-hexosaminidase subunit alpha (HEXA) - Tay Sachs disease (TSD) [42] | Neurodegeneration |
| 017 | 6dh0A | 3kciA (−9.3) | E3 ubiquitin-protein ligase (HERC2) - neurodevelopmental disorder [42] | Neurological complications |
| 017 | 3oxwB | 2r7eB (−7.6) | Coagulation factor VIII (C8) - hemophilia [43] | Increased risk of hemorrhage in hemophilia patients |
| RIT | 5veuA | 3d7uA (−8.5) | Tyrosine protein kinase (CSK) - suppress SRC tyrosine kinase (SFK) activity that cause cancer such as colorectal cancer [44] | Increased risk of colorectal cancer |
| RIT | 1rl8A | 3hhdA (−13.1) | Fatty acid synthase (FAS/FASN) - lipid mechanism [45] | Lipodystrophy |
| NPS | 2vdbA | 3fgqA (−6.1) | Neuroserpin (SERPIN1) - stroke [46] | Increased risk of stroke |
| LSN | 5x24A | 1kcwA (−7.4) | Ceruloplasmin (CP) - Parkinsonism [47] | Worsens the effects of parkinsonism |
| LSN | 5x24A | 3gzdA (−6.7) | Selenocysteine lyase (SCLY) - glucose and lipid metabolism [48] | Prevents metabolic syndromes |
| Potential off-targets with reported antiviral properties | ||||
| NPS | 4po0A | 1qm9A (−6.9) | Polypyrimidine tract-binding protein 1 (PTBP1) - allow viral replication through its RNA binding domain [49] | Potentially inhibit viral replication |
| AIN | 2qqtA | 1d7wC (−6.1) | Myloperoxidase (MPO) - antiviral properties toward influenza virus [50], induce secondary bacterial lung infection [51] | Potentially decrease lung viral loads |
| IMN | 3ogwA | 6azpA (−8.2) | ||
| RIT | 1rl8A | 3hhdA (−13.1) | Fatty acid synthetase (FAS/FASN) - facilitate viral replication through generation of membrane compartments [52] | Potentially inhibit viral replication |
1
Drug IDs are indicated as in Table 1.