Table 3.
Summary of NS2B/NS3 protease inhibitors recent development applying in silico method.
| Compound name | Method | Docking score (kcal/mol) | Closed-contact residues | Ref. | |
|---|---|---|---|---|---|
| 1 | Nimbin -Triterpenoids (From Azadirachta indica (neem)) |
i. Protein PDB ID: 2VBC ii.Ligands: Natural product compounds iii.Molecular docking program: MTiAutoDock |
–5.56 | His51, Asp75, Ser135, Asn152, Val36, Arg73, Pro132, Gly133, Gly153, Val154 | (Dwivedi et al., 2016) |
| 2 | Desacetylnimbin -Triterpenoids (From Azadirachta indica (neem)) |
–5.24 | Arg54, Gly133, Asn152, Val36, Trp50, His51, Val72, Arg73, Asp75, Pro132, Ser135 | ||
| 3 | Desacetylsalannin - Triterpenoids (From Azadirachta indica (neem)) |
–3.43 | Trp50, His51, His54, Val72, Arg73, Asp75, Asn152 | ||
| 4 | ZINC ID: 75163069 | i. Protein PDB ID: 2FOM ii. Ligands: Synthesized compounds from ZINC database iii. Pharmacophore modelling and Molecular docking program: Molecular Operating Environment (MOE) |
-19.98 | His51, Asp75, Ser135, Gly153, Gly151, Pro132, Val154, Leu128 | (Qamar et al., 2016) |
| 5 | ZINC ID: 59170698 | -18.26 | His51, Asp75, Ser135, Lyc73, Gly153, Pro132, Arg54 | ||
| 6 | ZINC ID: 06395655 | -20.08 | His51, Asp75, Gly153, Gly151, Pro132, Tyr161 | ||
| 7 | ZINC ID: 32933073 | -22.34 | His51, Asp75, Ser135, Pro132, Gly153, Ile36 | ||
| 8 | ZINC ID: 13728171 | -10.22 | His51, Asp75, Tyr161, Gly153, Pro132, Ile36, Leu128, Gly151 | ||
| 9 | ZINC ID: 65395833 | -19.89 | His51, Asp75, Gly151, Leu128, Gly153 | ||
| 10 | Baicalein (flavonoid) | i. Protein PDB ID: 2FOM ii. Ligands: Synthesized compounds iii. Pharmacophore modeling and Molecular docking program: AutoDock Vina 1.5.6, Discovery Studio 2.5 |
-7.5 | Lys74, Leu76, Asn152, Trp83, Leu149, Gly148, Glu88, Asn152, Leu149, Trp83 |
(Hassandarvish et al., 2016) |
| 11 | Baicalin (flavonoid) | -8.0 | Gly148, Leu149, Trp83, Leu76, Asn152, Trp86, Leu128, Tyr161, Arg54, Gly153, Tyr161, His51, Tyr150 | ||
| 12 | Meclofenamic acid (Compound 4) |
i. Protein: 3D homology model of NS2B-NS3 protease of DENV-2, namely DH-1 retrieved from Heh et al. (2013). ii. Ligands: Synthesized compound from PubChem iii. Molecular docking program: AutoDock |
-3.64 | His51, Gly151, Val155, Tyr161, Phe130, Ser131, Pro132, Thr134, Ser135, Tyr150, Asn152, Gly153, Val154 | (Othman et al., 2017) |
| 13 | Rolitetracycline (Compound 5) |
-3.21 | Gly153, Phe130, Gly151, Tyr161, Asn152, His51, Asp129, Thr134, Ser135, Tyr150, Val154, Pro132, Val155 | ||
| 14 | Uncinanone B (Plant flavonoid; C20H18O6) |
i. Protein PDB ID: 2FOM ii. Ligands: Natural product compounds from MAPS database Pubchem Zinc database, ChEBI, MPD3 and ChEMBL |
-12.156 | His51, Pro132, Asp75, Gly153, Leu128, Ser135 | (Qamar et al., 2017) |
| 15 | 5- hydroxybowdichione (Plant flavonoid; C16H10O7) |
-12.110 | His51, Tyr150, Asp75, Gly153, Ser135, Pro132, Leu128 | ||
| 16 | Prunetin (Plant flavonoid; C16H12O5) |
-11.369 | His51, Tyr150, Asp75, Gly153, Leu128, Pro132 | ||
| 17 | 5,7,3’,4’- tetrahydroxyisoflavone (Plant flavonoid; C21H20O11) |
-10.534 | His51, Pro132, Gly153, Leu128, Ser135, Asp75 | ||
| 18 | Alpinumisoflavone (Plant flavonoid; C20H16O5) |
-10.449 | His51, Gly153, Asp75, Pro132, Leu128 | ||
| 19 | Glicoisoflavanone (Plant flavonoid; C20H18O6) |
-10.015 | His51, Asp75, Pro132, Leu128, Gly153 | ||
| 20 | Fumaritine N-oxide (Fumaria indica) |
i. Protein PDB ID: 2FOM ii. Ligands: Natural product compounds from PubChem iii. Molecular docking program: AutoDock Vina |
-9.2 | His51, Arg54, Val72, Asp75, Asn152 | (Rasool et al., 2018) |
| 21 | Osajin (Erythrina variegate) |
-9.7 | Leu128, Phe130, Pro132, Tyr150, Gly151, Gly153 | ||
| 22 | SigmodinA | -9.0 | His51, Leu128, Pro132 | ||
| 23 | SigmodinB | -9.4 | His51, Asp75, Leu128, Pro132, Val154 | ||
| 24 | SigmodinC | -9.4 | His51, Asp75, Leu128, Pro132, Ser135, Gly153 | ||
| 25 | SKYa 4-Thiazolidinone coumarin derivatives | i. Protein PDB ID: 2FOM ii. Ligands: Synthesized compounds iii. Molecular docking program: Receptor Grid Generation™ |
-2.754 | His51, Asp75, Tyr150, Gly151, Asn152, Gly153, Ser135, Pro132, Ser131, Phe130, Leu128 | (Yusufzai et al., 2018a) |
| 26 | SKYb 4-Thiazolidinone coumarin derivatives | -2.960 | Asp75, Val154, Gly153, Asn152, Gly151, Tyr150, His51, Leu128, Phe130, Ser131, Pro132, Ser135 | ||
| 27 | SKYc 4-Thiazolidinone coumarin derivatives | -3.905 | His51, Gly153, Gly151, Tyr150, Leu128, Phe130, Ser131, Pro132, Ser135 | ||
| 28 | Quercetin 3-O-(2′′,3′′-digalloyl)-β-D-galactopyranoside (Euphorbia lunulata) |
i. Protein PDB ID: 2FOM ii. Ligands: Natural product compounds from Chebi database iii. Molecular docking program: Molecular Operating Environment (MOE) |
-26.101 | Gly87, Val146, Asn167 | (Sarwar et al., 2018) |
| 29 | Quercetin 3-O-α- (6′′’-caffeoylglucosyl-β-1,2-rhamnoside) (Sedum sarmentosum) |
-24.987 | Lys74, Ile165 | ||
| 30 | Schaftoside (Passiflora tripartita) |
-23.399 | Trp83 | ||
| 31 | Myricetin (Myrica rubra) |
-21.987 | Trp83, Gly87, Val146 | ||
| 32 | Quercetin 3-sulfate (Anethum graveolens) |
-20.989 | Lys74 | ||
| 33 | Eriocitrin (Citrus lumia, Cyclopia subternata) |
-20.693 | Lys74 | ||
| 34 | Catiguanin B (Trichilia catigua) |
-20.414 | Lys74, Trp83 | ||
| 35 | 4′,5,7-trihydroxy-3-methoxyflavone-7-O- α-L-arabinofuranosyl(1 → 6)-β-D-glucopyranoside (Lepisorus contortus) |
-20.378 | Asn67, Val47, Trp89 | ||
| 36 | Wogonin 7-O-β-D-glucuronide (Scutellaria baicalensis) |
-20.102 | Gly87, Trp83 | ||
| 37 | Silychristin (Silybum marianum) |
-20.085 | Lys74, Trp83 | ||
| 38 | (E)-7-Hydroxy-3-(1-(2-(4-p-tolylthiazol-2-yl)hydrazono) ethyl)-2H-chrom-en-2-one (Compound 7c) |
i. Protein PDB ID: 2FOM ii. Ligands: Synthesized compounds iii. Molecular docking program: Receptor Grid GenerationTM |
-5.141 | Ser131, Pro132, Ser135, Gly151, Gly153, Asp75, Val72, Trp50, His51, Tyr161, Leu128, Tyr150 | (Yusufzai et al., 2018b) |
| 39 | (E)-7-Methoxy-3-(1-(2-(4-phenylthiazol-2-yl)hydrazono) ethyl)-2H-chromen-2-one (7l) (Compound 7l) |
-3.894 | Gly153, Asp75, Val154, Leu154, Leu128, Phe130, Tyr150, Ser131, Pro132, Ser135, Gly151, Val72, Lys73 | ||
| 40 | Indanone derivatives (Compound 3g) |
i. Protein: Homologous crystal structure by Wichapong et al. (2010) ii: Ligand: Synthesized compounds iii. Molecular docking program: AutoDock 4.2 |
–7.3 | Gly82, His51, Tyr161 | (Nesfu et al., 2019) |
| 41 | Indanone derivatives (Compound 3h) |
–7.3 | Asn154, His51, Tyr161 | ||
| 42 | Ganodermanotriol (Triterpenoids of Ganoderma lucidum) |
i. Protein PDB ID: 2FOM ii: Ligand: Natural product compounds iii. Molecular docking program: Schrodinger |
−6.291 | Lys73, Thr120, Asn167, Trp50, Val72, Ile123, Val154, Val155, Ala164, His51, Thr118, Asn119, Asn152, Gly153, Lys74, Asp75 | (Bharadwaj et al., 2019) |
| 43 | Canthin-6-one 9-O-beta-glucopyranoside | i. Protein PDB ID: 2FOM ii: Ligand: Natural product compounds from MPD3 database, MAPS database, Pubchem and Zinc database iii. Molecular docking program: MOE |
−15.17 | His51, Asp75, Ser135, Gly151, Gly153, Asn152, Leu128, Tyr150 | (ul Qamar et al., 2019) |
| 44 | Kushenol W | -14.55 | His51, Ser135, Gly151, Gly153, Asp75, Tyr161, Leu128, Asn152, Pro132, Phe130 | ||
| 45 | Kushenol K | −16.39 | His51, Ser135, Pro132, Tyr150, Asp75, Gly153, Leu128, Gly151, Asn152, Phe130 | ||
| 46 | (3E,5E)-3,5-bis(4-methoxybenzylidene)-1-(phenylsulfonyl) piperidin-4-one (Compound 2) |
i. Protein PDB ID: 2FOM ii: Ligand: Synthesized compounds iii. Molecular docking program: AutuDock |
-61.01 | Gly51, Arg54, Pro132, His51, Asp75 and Ser135 | (Ikhtiarudin, 2019) |
| 47 | Orientin (Phytoconstituents of Cynodon dactylon) |
i. Protein PDB ID: 3U1I ii: Ligand: Natiral product compounds from PubChem iii. Molecular docking program: FlexX Lead IT 2.3. |
-21.9439 | Asn B:152, Tyr B:16, Gly B:151, Gly B:153, Phe B:130, Lys B:131, Arg B:54, His B:51 |
(Chandani et al., 2019) |
| 48 | Triglochinin (Phytoconstituents of Cynodon dactylon) |
-29.0361 | Gly B:153, Gly B:133, Gly B:151 | ||
| 49 | Apigenin (Phytoconstituents of Cynodon dactylon) |
-26.2859 | His B: 51, Phe B:130, Tyr B:150, Ser B:135 | ||
| 50 | Luteolin (Phytoconstituents of Cynodon dactylon) |
-29.4214 | Lys B:131, Tyr B:150, Gly B:153 | ||
| 51 | Fluorinated pyrazoline analogue (Compound 1) |
i. Protein PDB ID: 2FOM ii: Ligand: Synthesized compound iii. Molecular docking program: MOE |
−59.98 | His51, Arg74 Asp75 His51, Arg | (Zamri et al., 2019) |
| 52 | Coumarin derivatives (Compound Vb) |
i. Protein PDB ID: (ND) ii: Ligand: Synthesized compound iii. Molecular docking program: iGEMDOCK |
-104.22 | Gly151, Tyr150 | (Tataringa et al., 2019) |
| 53 | Luteolin (Phytochemical of Carica papaya) |
i. Protein PDB ID: 2FOM ii: Ligand: Natural product compound iii. Molecular docking program: PyRx software (Version 0.8) |
-7.7 | Asp75, Gly153, Ser131, Leu128, Phe130, Tyr150 | (Ghosh and Talukdar, 2019) |
| 54 | Epigallocatchin (Carica papaya bioactive compound) |
i. Protein PDB ID: (ND) ii: Ligand: Natural product compounds iii. Molecular docking program: MOE |
−13.2911 | His51, Asp75, Ser135, Val72, Lys73, Tyr135, Gly151 | (Farooq et al., 2020) |
| 55 | Catechin (Carica papaya bioactive compound) |
−9.0122 | His51, Asp75, Ser135, Val72, Lys73, Tyr135, Gly151 | ||
| 56 | Protocatechuric acid (Carica papaya bioactive compound) |
-7.5592 | His51, Asp75, Ser135, Val72, Lys73, Tyr135, Gly151 | ||
| 57 | C25H21N5O3
(Compound A1) |
i. Protein PDB ID: 2FOM ii: Ligand: Synthesized compounds from Asinex database iii. Molecular docking program: AutoDock Vina |
-10.86 | Thr120, Asn152, Asn167, Val72, Leu76, Ile123, Leu76 | (Bhowmick et al., 2020) |
| 58 | C21H19FN6O2
(Compound A2) |
-11.07 | Asn167, Asn152, Lys73, Leu76, Al164 | ||
| 59 | C23H20N6O2
(Compound A3) |
-10.97 | Lys73, Asn152, Asn167, Lys74, Leu76, Ile123, Ala164 | ||
| 60 | C21H19FN4O4
(Compound A4) |
-10.71 | Lys73, Gly153, Asn167 Lys74, Leu76 | ||
| 61 | C28H35N5O4
(Compound A5) |
-10.33 | Thr120, Asn152, Gly153 | ||
| 62 | CAA15 | i. Protein PDB ID: Model - homologous crystal structure of DENV-2 NS2B/NS3pro ii: Ligand: Synthesized compounds from Asinex database iii. Molecular docking program: AutoDock 4.2 |
-7.22 | Ile36, His51, Al52, Asp29, Phe130, Pro132, Tyr161 | (Puc et al., 2021) |
| 63 | CAA16 | -7.03 | Ile36, His51, Val52, Asp29, Phe130, Pro132, Tyr161 | ||
| 64 | CAA17 | -7.07 | Val52, Arg54, Asp29, Phe130, Pro132, Tyr161 |