Progress in the Identification of Dengue Virus Entry/Fusion Inhibitors

Table 1

Inhibitors of dengue virus entry.

Compound	Remarks	Cell line	Dengue virus serotype	IC50/EC50^#	Reference
1OAN1	Fusion inhibitor, peptide based on E protein domain II hinge	LLCMK2	DENV-2	IC50: 7±1 𝜇M^3	[96]
DN57opt	Fusion inhibitor, peptide based on E glycoprotein DI/DII beta sheet connection	LLCMK2	DENV-2	IC50: 8±1𝜇M^3	[96]
DN59	Fusion inhibitor, E glycoprotein stem and E trimer binder, peptide based on stem sequence	LLCMK2	DENV-2	IC50: 2–5 𝜇M^1	[84, 85]
Compound 6	Fusion inhibitor, E glycoprotein hydrophobic pocket binder	A549/BHK21	All	EC50: 0.068–0.49 𝜇M^1∗	[91]
Rolitetracycline	Fusion inhibitors, tetracycline derivative, and E glycoprotein hydrophobic pocket binder	BHK21	DENV-2	IC50: 67 𝜇M^2	[88]
Doxycycline	Fusion inhibitors, tetracycline derivative, and E glycoprotein hydrophobic pocket binder	BHK21	DENV-2	IC50: 55 𝜇M^2	[87]
NITD448	Fusion inhibitor, E glycoprotein hydrophobic pocket binder	BHK21	DENV-2	EC50: 9.8 𝜇M^3; IC50: 6.8 𝜇M	[92]
A5	E glycoprotein hydrophobic pocket binder	Vero	DENV-2	IC50: 1.2 𝜇M^2	[93]
1662G07 and derivatives	Fusion inhibitor, E glycoprotein stem, and E trimer binders	BHK21	DENV-2	IC50: 8 𝜇M^1	[87]
SA-17	Derivative of doxorubicin, possible E glycoprotein hydrophobic pocket binder	Vero/BHK21	DENV-1; DENV-2; DENV-3	EC50: 12𝜇M^4; EC50: 1.2𝜇M^4; EC50: 1.7𝜇M^4	[89]
LCTA-949	Analogue of the antibiotic teicoplanin, entry inhibitor	Vero	DENV-2	EC50: 6.9𝜇M^1	[90]
ST-148	Inhibitor of capsid protein, effective in animal model	Vero	All	EC50: 0.016–2.8 𝜇M^4	[109]
E 419-447 peptides	Stem derived sequence, trimer binder	BHK	DENV-2	IC90: 0.1–6 𝜇M^2	[86]
E 380-389 peptides	Domain III derived sequence, attachment inhibitor	LLCMK2	DENV-2	IC50: 35 𝜇M^2	[98]
P02	Binds to DENV hydrophobic pocket	BHK	YFV-IRES-Luc	IC50: 13±3𝜇M^8	[95]
HHA, GNA, and UDA	Carbohydrate binding agent	Raji/DC-SIGN^+	All	EC50: 4.6; 3.8; 0.29 nM^5	[73]
Pradimicin-S	Carbohydrate binding agent	Dendritic cells	DENV-2	EC50: 11 𝜇M^5	[73]
PI-88, suramin, and pentosan polysulfate	Heparan mimetic	BHK	DENV-2	EC50: 200 𝜇g/mL^9∗	[105]
Fucoidan	Heparan mimetic	BHK21	DENV-2	IC50: 4.7 𝜇g/mL^3	[99]
Sulfated galactomannan	Heparan mimetic	C6/36	DENV-1	EC50: 200 mg/L^10∗	[106]
DL-galactan	Heparan mimetic	Vero	DENV-2	IC50: 0.9–1 𝜇g/mL^1	[103]
Iota-carrageenan	Heparan mimetic	Vero	DENV-2	EC50: 0.4𝜇g/mL^1	[103]
Zosteric acid, CF-238	Heparan mimetic	LLCMK2	All	IC50: 14–47 𝜇M^3	[110]
Curdlan sulfate	Heparan mimetic	LLCMK2	DENV-2	EC50: 7𝜇g/mL^6	[101]
Sulfated galactan, sulfated xylomannan	Heparan mimetic	Vero	All	IC50: 0.12–20 𝜇g/mL^1	[102]
Sulfated K5 polysaccharide	Heparan mimetic	HMEC-1	DENV-2	EC50: 111 nM^9	[104]
Chebulagic acid, punicalagin	Hydrolysable tannins	Vero	DENV-2	EC50: 13.1 and 7.8 µM^7	[108]
Chondroitin sulfate E	Heparan mimetic	BHK21	All	EC50: 0.3 µg/mL^3	[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.
¹⁰Immunofluorescens.
*Tested in vivo in animal model.