BioMed Research International / 2014 / Article / Tab 1

Review Article

Progress in the Identification of Dengue Virus Entry/Fusion Inhibitors

Table 1

Inhibitors of dengue virus entry.

CompoundRemarksCell lineDengue virus serotype Reference

1OAN1Fusion inhibitor, peptide based on E protein domain II hingeLLCMK2DENV-2IC50: M3[96]

DN57optFusion inhibitor, peptide based on E glycoprotein DI/DII beta sheet connectionLLCMK2DENV-2IC50: M3[96]

DN59Fusion inhibitor, E glycoprotein stem and E trimer binder, peptide based on stem sequenceLLCMK2DENV-2IC50: 2–5  M1[84, 85]

Compound 6Fusion inhibitor, E glycoprotein hydrophobic pocket binderA549/BHK21AllEC50: 0.068–0.49  [91]

RolitetracyclineFusion inhibitors, tetracycline derivative, and E glycoprotein hydrophobic pocket binderBHK21DENV-2IC50: 67  M2[88]

DoxycyclineFusion inhibitors, tetracycline derivative, and E glycoprotein hydrophobic pocket binderBHK21DENV-2IC50: 55  M2[87]

NITD448Fusion inhibitor, E glycoprotein hydrophobic pocket binderBHK21DENV-2EC50: 9.8  M3
IC50: 6.8  M

A5E glycoprotein hydrophobic pocket binderVeroDENV-2IC50: 1.2  M2[93]

1662G07 and derivativesFusion inhibitor, E glycoprotein stem, and E trimer bindersBHK21DENV-2IC50: 8  M1[87]

SA-17Derivative of doxorubicin, possible E glycoprotein hydrophobic pocket binderVero/BHK21DENV-1 
EC50: 12 M4
EC50: 1.2 M4
EC50: 1.7 M4

LCTA-949Analogue of the antibiotic teicoplanin, entry inhibitorVeroDENV-2EC50: 6.9 M1[90]

ST-148Inhibitor of capsid protein, effective in animal modelVeroAllEC50: 0.016–2.8  M4[109]

E 419-447 peptidesStem derived sequence, trimer binderBHKDENV-2IC90: 0.1–6  M2[86]

E 380-389 peptidesDomain III derived sequence, attachment inhibitorLLCMK2DENV-2IC50: 35  M2[98]

P02Binds to DENV hydrophobic pocketBHKYFV-IRES-LucIC50: M8[95]

HHA, GNA, and UDACarbohydrate binding agentRaji/DC-SIGN+AllEC50: 4.6; 3.8; 0.29 nM5[73]

Pradimicin-SCarbohydrate binding agentDendritic cellsDENV-2EC50: 11  M5[73]

PI-88, suramin, and pentosan polysulfateHeparan mimeticBHKDENV-2EC50: 200  [105]

FucoidanHeparan mimeticBHK21DENV-2IC50: 4.7  g/mL3[99]

Sulfated galactomannanHeparan mimeticC6/36DENV-1EC50: 200  [106]

DL-galactanHeparan mimeticVeroDENV-2IC50: 0.9–1  g/mL1[103]

Iota-carrageenanHeparan mimeticVeroDENV-2EC50: 0.4 g/mL1[103]

Zosteric acid, CF-238Heparan mimetic LLCMK2AllIC50: 14–47  M3[110]

Curdlan sulfateHeparan mimeticLLCMK2DENV-2EC50: 7 g/mL6[101]

Sulfated galactan, sulfated xylomannanHeparan mimeticVeroAllIC50: 0.12–20  g/mL1[102]

Sulfated K5 polysaccharideHeparan mimeticHMEC-1DENV-2EC50: 111 nM9[104]

Chebulagic acid, punicalaginHydrolysable tanninsVeroDENV-2EC50: 13.1 and 7.8 µM7[108]

Chondroitin sulfate EHeparan mimeticBHK21AllEC50: 0.3 µg/mL3[81]

IC50/EC50: in antiviral assays, half maximal effective concentration (EC50) refers to the concentration of compound causing 50% reduction of virus replication in cell based assays. Half maximal inhibitory concentration (IC50) is used when virus inhibition is estimated from in vitro inhibition assays, such as the inhibition of a viral enzyme. Sometimes both EC50 and IC50 values are used loosely to describe the same antiviral activity. In this review, we are following the original nomenclature used by each cited paper.
1Viral plaque reduction assay.
2Plaque formation assay.
3Focus forming assay.
4Virus induced CPEs.
5RNA quantitation.
6Cell viability.
7Viral EGFP (enhanced green fluorescent protein) expression.
8Reduction of luciferase activity.
9Flow cytometry.
*Tested in vivo in animal model.