Table 3.
Various integrated VS approaches from the recent publications.
| Approaches | Databases Used for Studies | Target Proteins | Number of Hits Identified | Activities Types and Ranges | References |
|---|---|---|---|---|---|
| Sequential integration approaches | |||||
| Sequential combination of 2D similarity search, pharmacophore, and molecular docking | Zinc-Specs Database (441,574 compounds) | Human vascular endothelial growth factor receptor-2 (VEGFR-2) | 2 hits | Inhibitory effects on the proliferation of cancer cells (U87 and MCF-7) expressing VEGFR-2. | Ai et al. [19] |
| Sequential approach, including 2D pharmacophore-based and structural fingerprints, ADME/Tox filtering and flexible docking | Commercial and academic libraries (58 reference ligands) | 5-HT6R (serotonin 5-HT6 receptor) | 6 hits | Competition binding for human serotonin 5-HT6R, 5-HT2aR, 5-HT1aR, 5-HT7R and dopaminergic D2R | Staron et al. [20] |
| Integrated in silico screening sequence (2D similarity followed by docking) | CHEMBL database, ZINC database, FDA approved drugs; molecules under clinical trials (5M compounds) | SARS-CoV-2 main protease | 4 potential inhibitors | Inhibitory effect against SARS-CoV-2 main protease | Pant et al. [21] |
| Reverse virtual screening method: (A) VS. for identify novel scaffolds (B) 2D similarity search for hit expansion |
SPECS; PKU-CNCL (Peking University) | Glycogen synthase kinase-3b (GSK-3b) | 14 hits (IC50 = 0.71–18.2 μM) | Inhibitory effect against glycogen synthase kinase-3b (GSK-3b) | Dou et al. [22] |
| Sequential virtual screening: combination of 2D fingerprint matching and 3D shape modelling | CHEMBL database, FDA approved drugs | Human ether-a-go-go-related gene (hERG) | high recovery rate, maximum sensitivity, and specificity in hERG inhibition prediction | Blocking effect on human ether-a-go-go-related gene (hERG) | Schyman et al. [23] |
| Parallel integration approaches | |||||
| Parallel screening with ligand- and structure-based and virtual screening approaches | 6.6 M commercial compounds for LB 1.3 M compound for docking | Leucine rich repeat kinase-2 (LRRK2) | 35 compounds with IC50 < 10 μM | Inhibitory effect on leucine rich repeat kinase-2 (LRRK2) | Gancia et al. [24] |
| Parallel 2D similarity and pharmacophore-based virtual screening | SPECS | Fibroblast growth factor receptor 1 (FGFR1) | 19 compounds with activity >50% at 50 μM | Inhibitory effect on fibroblast growth factor receptor 1 (FGFR1) | Gagic et a.l. [25] |
| Parallel 2D/3D similarity search | Pubchem | Diacylglycerol kinase alpha (DGKalpha) | 17 active compounds with activity >25% at 10 μM | Inhibitory effect on Diacylglycerol kinase alpha (DGKalpha) | Velnati et al. [26] |
| Parallel hierarchical protocol combining ligand-based (2D similarity/pharmacophore model) and SB approaches for VS | DUD-E | Protein tyrosine phosphatase 1B (PTP1B) | 10 compounds with IC50 at micromolar level | Inhibitory effect on protein tyrosine phosphatase 1B (PTP1B) | Yan et al. [27] |
| Hybrid integration approaches | |||||
| Hybrid integration protocol (molecular modeling methods: molecular docking, molecular dynamics simulation) | ZINC DB | Histamine H3 receptor | 3 hits within micromolar and sub micromolar Ki range | Histamine H3 receptor antagonism | Ghamari et al. [28] |
| 2D similarity searching, docking and scoring | PubChem library (100 M) | Histone deacetylase (HDAC) | 60 virtual hit compounds; 4 active compounds | Inhibitory effect on histone deacetylase | Divsalar et al. [29] |