Table 1.
List of DENV inhibitors isolated by targeting host process. LLC-MK2 = rhesus monkey kidney cell, BHK = baby hamster kidney, GAG = glycosaminoglycan, DC-SIGN = dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin, MEK = MAPK/extracellular receptor kinase (ERK) kinase, NTRK1 = neurotrophic receptor tyrosine kinase 1, MAPKAPK = MAP kinase-activated protein kinase, RIG-I = retinoic-acid inducible gene I, IMP dehydrogenase = Inosine-5′-monophosphate dehydrogenase.
| Host Process | Inhibitor(s) | Target | DENV Types | Cell Line(s) Tested | Refs. |
|---|---|---|---|---|---|
| Glycolytic pathway | 2-deoxy-d-glucose (2DG) | Glycolysis | DENV-2 | HFFs Cell | [5] |
| Oxamate | Glycolysis | DENV-2 | HFFs Cell | [5] | |
| Lipid biosynthesis pathway | Cerulenin | Fatty acid biosynthesis | DENV-2 | Huh-7.5 Cell | [156,157] |
| C75 | Fatty acid biosynthesis | DENV-4 | C6/36 Cell | [156,157] | |
| Lovastatin (fluvastatin, lovastatin, mevastatin, and simvastatin) | Cholesterol biosynthesis | DENV-2 | Huh-7 Cell | [158,159] | |
| U18666A | Cholesterol biosynthesis | DENV-2 | C6/36 cell line | [160] | |
| Methyl b-cyclo dextrin | Cholesterol biosynthesis | DENV-1 to 4 | Huh-7 Cell | [158] | |
| Nordihydroguaiaretic acid | Fatty acid biosynthesis | DENV-4 | Huh-7 cell | [161] | |
| Orlistat | Fatty acid biosynthesis | DENV -4, -2 | HepG2 and HEK293T/17 Cell | [161] | |
| PF-429242 | Fatty acid biosynthesis | DENV-1–4 | Huh-7.5.1 Cell | [162] | |
| Hymeglusin | Cholesterol biosynthesis | DENV-2 | K562 cells | [68] | |
| Zaragozic acid | Cholesterol biosynthesis | DENV-2 | K562 cells | [68] | |
| Nucleotide biosynthesis pathways | Ribavirin | IMP dehydrogenase | DENV-2 | LLC-MK2 | [163] |
| N-ally acridones | IMP dehydrogenase (Partial) | DENV-2 | Vero cells | [163] | |
| Brequinar | Dihydroorotate dehydogenase | DENV-2 | Vero cells | [164] | |
| Mycophenolic acid | IMP dehydrogenase | DENV-2 | Huh-7, CRL-8024, and HepG2 | [165] | |
| NITD 982 | Dihydroorotate dehydogenase | DENV-2 | Vero cells | [69] | |
| ETAR | IMP dehydrogenase | DENV-2 | Vero cells | [166] | |
| IM18 | IMP dehydrogenase | DENV-2 | Vero cells | [166] | |
| Glycosaminoglycans | PI88 | Heparan sulfate | DENV-2 | BHK and in mice | [80] |
| Chondroitin sulfate | Heparan sulfate | DENV-1–4 | BHK-21 and Vero cells | [78] | |
| Curdlan sulfate | Heparan sulfate | DENV-1–4 | LLC-MK2 cells | [77] | |
| K5 polysaccharide from Escherichia coli | Heparan sulfate | DENV-2 | HMEC-1 and HMVEC-d cells | [83] | |
| Heparin | Heparan sulfate | DENV-2 | Vero, BHK, Hepatocytes | [79] | |
| Fucoidans | Heparan sulfate | DENV-2 | BHK | [82] | |
| GAG | Heparan sulfate | DENV-2 | Vero | [79] | |
| Sulfated galactomannan | Heparan sulfate | DENV-1 | C6/36 | [167] | |
| DL-galactan | Heparan sulfate | DENV-2, -3 | Vero, Hep-G2 | [141] | |
| Carrageenan | Heparan sulfate | DENV-2, -3 | Vero, Hep-G2 | [138] | |
| α-d-glucan | Heparan sulfate | DENV-2 | BHK | [84] | |
| Dextran sulfate 8000 | Heparan sulfate | DENV-2 | Hepatocytes, Vero | [168] | |
| Zosteric acid, CF-238 | Heparan sulfate | DENV-1–4 | LLC-MK2 | [77] | |
| DC-SIGN | PRM-S | Carbohydrate binding agent | DENV-2 | Raji/DC-SIGN and MDDC | [169] |
| QL-XII-47 (QL47) | DC-SIGN(BTK) | DENV-2 | Huh-7 Cell | [170] | |
| Plant lectins from Hippeastrum hybrid, Galanthus nivalis, Urtica dioica | DC-SIGN | DENV-1–4 | MDDC, Huh-7, U87/DC-SIGN | [169] | |
| Glycomimetic DC-SIGN ligand | DC-SIGN | DENV-2 | DC-SIGN/Raji cells | [171] | |
| DS (MW > 500,000 Da) | DC-SIGN | DENV-1–4 | C6/36 | [169] | |
| Host protease | 45 | Furin | DENV-2 | Huh-7 cells | [172] |
| 46 | Furin | DENV-2 | Huh-7 cells | [172] | |
| Peptidomimettic furin inhibitor, Luteolin | Furin | DENV-1–4 | Huh-7 cells | [105] | |
| Host kinase | Dasatinib | c-Src/Fyn | DENV-1–4 | Vero, Huh-7 | [106] |
| SaracatinibAZD0530 | c-Src/Fyn | DENV-1–4 | Vero, Huh-7 | [106] | |
| GNF-2 | Abl Kinases E Protein | DENV-2 | BHK-21 | [108] | |
| Imatinib | Abl Kinases | DENV-2 | BHK-21 | [108] | |
| Mitogen activated protein kinase | PD98059, U0126, FR180204 | MEK | DENV-2 | RAW264.7 | [173] |
| SB203580 | p38 pathway | DENV-2 | C6/36 | [174] | |
| CGP57380 | ERK and p38 pathways | DENV-2 | BHK-21 | [175] | |
| Imidazo[1,2-b] pyridazine | AAK1 | DENV-2 | Huh-7 | [176] | |
| Isothiazolo[5,4-b] pyridines | GAK | DENV-2 | Huh-7 | [177] | |
| Sunitinib and erlotinib | AAK1 and GAK | DENV-2 | Huh7 | [178] | |
| AR-12 | PI3K/JAKT pathway | DENV-1–4 | Huh 7 | [179] | |
| U0126 | Erk inhibitor | DENV-2, -3 | BHK-21 | [180] | |
| SFV785 | NTRK1 and MAPKAPK5 | DENV-2 | BHK-21 | [108] | |
| Host Glucosidase | CM-9-78 (DNJ derivative) | α-glucosidase | DENV-1 to 4 | BHK-21 | [181] |
| UV-4 (DNJ derivative) | α-glucosidase | DENV-2 | BHK-21 | [117] | |
| DNJ | α-glucosidase | DENV-1 | BHK-21 | [117] | |
| Celgosivir | α-glucosidase | DENV-1–4 | BHK | [116] | |
| Kotalanol | α-glucosidase | DENV-1–4 | BHK | [86] | |
| Castanospermine | α-glucosidase | DENV-1–4 | BHK, Huh-7 | [110,112] | |
| OSL-9511 | α-glucosidase | DENV-2 | BHK | [182] | |
| NN-DNJ | α-glucosidase | DENV-2 | BHK | [114] | |
| Compound 36 | α-glucosidase | DENV-2 | BHK-21 | [183] | |
| Compound 36 | α-glucosidase | DENV-2 | BHK-21 | [183] | |
| Compound 36 | α-glucosidase | DENV-2 | BHK-21 | [183] | |
| N-alkyl side chains 69(CST) | α-glucosidase | DENV-2 | BHK | [183] | |
| N-alkyl side chains 70(DNJ) | α-glucosidase | DENV-2 | BHK | [183] | |
| N-alkyl side chains 71 | α-glucosidase | DENV-2 | BHK | [182] | |
| N-alkyl side chains 72 | α-glucosidase | DENV-2 | BHK | [182] | |
| N-alkyl side chains 73 | α-glucosidase | DENV-2 | BHK | [182] | |
| N-alkyl side chains 74 | α-glucosidase | DENV-2 | BHK | [184] | |
| N-alkyl side chains 75 | α-glucosidase | DENV-2 | BHK | [184] | |
| N-alkyl side chains 76 | α-glucosidase | DENV-2 | BHK | [184] | |
| N-alkyl side chains 77 | α-glucosidase | DENV-2 | BHK | [185] | |
| N-alkyl side chains 78 | α-glucosidase | DENV-2 | BHK | [117] | |
| N-alkyl side chains 79 | α-glucosidase | DENV-2 | BHK | [186] | |
| SP173 | α-glucosidase | DENV-2 | BHK-21 | [112] | |
| SP169 | α-glucosidase | DENV-2 | BHK-21 | [112] | |
| 6-O-butanoyl castanospermine | α-glucosidase | DENV-2 | BHK-21 | [110] | |
| Host Immunity, and Inflammatory pathways | Human heme oxygenase I | Innate antiviral response | DENV-1–4 | Huh-7 | [187] |
| Schisandrin A | STAT1/2-mediated responses | DENV-1–4 | Huh-7 | [188] | |
| Celastrol | JAK–STAT signaling | DENV-1–4 | Huh-7 | [189] | |
| Agonists of IRF3-terminal pathways | TRIF Pathway | DENV-2 | Vero cells | [190] | |
| Salidroside | RIG-I | DENV-2 | THP-1 cell line | [191] | |
| Asunaprevir | MAVS pathways | DENV-2 | Huh 7.5.1, Hep-G2 cells, | [192] | |
| Sequence-specific RIG-I agonist | IRIG-I-mediated | DENV-2 | Lung epithelial A549 cells | [193] | |
| Helicase with zinc linger 2 | Innate antiviral response | DENV-2 | Vero cells | [194] | |
| Purinergic receptor P2X7 | Inflammatory process | DENV-2 | Human monocyte Cell | [195] | |
| Extract from Uncaria tomenrosa, N. brasiliensis Choisy, Uncaria guianensis | Cytokine/chemokine | DENV-2 | Huh-7 | [196,197] | |
| Extract from Cissampelos pareira Linn | Innate antiviral response | DENV-1–4 | C6/36, LLC-MK2, Vero, Hep-G2 | [198] | |
| Ivermectin | α/β-mediated transport | DENV-1–4 | HeLa | [198] | |
| BST2/tetherin | IFN induced | DENV-2 | Huh7 | [199] |