Table 1 Post-entry host-directed DENV antivirals
Stage | Compound | DENV serotype | IC50/ (90) | SI:CC50/IC50 | Reference |
|---|---|---|---|---|---|
Translation | NITD451 | DENV2 | 0.16 µM (A549) | >50 | |
Bromocriptine | DENV1 DENV2 DENV3 DENV4 | 1.6 µM (BHK 21) 1.2 µM 0.8 µM 0.8 µM | >33 | ||
Lactimidomycin | DENV2 | 0.40 µM (IC90, Huh7) | / | ||
ST081006 | DENV2 | 3.14 µM (Huh7) | 8.03 | ||
Narasin | DENV1 DENV2 DENV3 DENV4 | 0.65 µM (Huh7) 0.39 µM 0.44 µM 0.05 µM | >2500 | ||
AR-12 | DENV2 | 0.59 µM (A549) | 142 | ||
Catechin | DENV1 DENV2 DENV3 DENV4 | 37.94 µM (Huh7) 6.42 µM 38.95 µM 16.83 µM | >15.57 (DENV2) | ||
Translocation | Cotransin 8 PS3061 | DENV2 | Active at 0.5 µM (Huh7 + C6/36), at 0.1 and 0.5 µM (MDDCs) Active at 1 µM (Huh7 + C6/36) | / | |
Apratoxin S4 | DENV2 | 0.003 µM (Huh7.5) | >300 | ||
Signal peptidase cleavage | Cavinafungin | DENV1 DENV2 DENV3 DENV4 | 0.004 µM (A549) 0.005 µM 0.003 µM 0.003 µM | 160 | |
Glycosylation/folding | NGI-1 | DENV2 | 0.85 µM (HEK293T) | 41 | |
Castanospermine | DENV2 | 85.7 µM (Huh7) 1 µM (BHK-21) | / | ||
Celgosivir | DENV1 DENV2 DENV3 DENV4 | 0.65 µM (BHK-21) 0.22 µM 0.68 µM 0.31 µM | |||
Deoxynojirimycin derivatives, UV-4B | DENV1 | 5–38 µM (Vero) | >11.6–>477 | ||
DENV2 DENV3 DENV4 | 6–22 µM 4–86 µM 3–18 µM | ||||
UV12 | DENV2 | 22 µM (Vero) | >22 | ||
Iminocyclitol (36-37-38) | DENV2 | 4.7–11.8 µM (BHK-21) 9–18 µM (IC90) | >0.8–>2 | ||
Sulfonium ions | DENV2 | 25.1–50.4 µM (Vero) | >3 >1 | ||
Valiolamine derivates | DENV2 | 1.38 µM (Vero) | 88 | ||
AR-12 | DENV2 | 0.59 µM | 142 | ||
JG40 | DENV2 | /(Huh7, C6/36) | / | ||
ER rearrangement | |||||
VP and CM biogenesis | CB-5083 NMS-873 | DENV2luc. | 0.25 µM (Huh7.5) 0.02 µM | 100 1250 | |
Cholesterol synthesis | Statins, Lovastatin | DENV2 DENV2luc. | >50 µM (K526) 1.8–46 µM (A549) | <1 <5 | |
Atorvastatin | DENV2 DENV4 | 24.1 (Huh-7) 12.2 µM | 2.35 1.67 | ||
Metformin | DENV2 DENV1 DENV2 DENV3 DENV4 | 3.82 µM (Huh7) 3108 µM (BHK-21) 4300 µM 3139 µM 3068 µM | 8.61 / | ||
PF-429242 PF-06409577 | DENV2 | 6.7 µM (Hela) 13.4 µM (Vero) | 35 43.4 | ||
Compound C | DENV2 HepG2 | / | / | ||
Nordihydroguaiaretic Acid | / | / | / | ||
Hymeglusin | DENV2 | 4.5 µM (K526) | 11 | ||
U18666A | DENVluc. | 6.2 µM (A549) 2.9 µM (Huh7) | 11 12 | ||
Squalene synthesis | Zaragozic acid | DENV2 | 8.3 µM (K526) | 6 | |
Cholesterol transport | Ezetimibe | DENV1 DENV2 DENV3 DENV4 | 19.2 µM (Huh7) 13.4 µM 24.2 µM 17.7 µM | 2.93 (DENV2) | |
Fatty acid synthesis | C75, Cerulenin | DENV2 | ~1 µM (Huh7) | / | |
Orlistat | / | / | / | ||
PF-05175157, PF-05206574, PF-06256254 | DENV2 | 1.0 µM (Vero) <1.3 µM 1.5 µM | 236 319 135 | ||
RNA synthesis | |||||
Inosine monophosphate dehydrogenase | Ribavirin, | DENV2 | 73 µM (Vero), 38 µg/ml, 40 µM (Huh7), | >13, / / | |
ETAR, IM18, EICAR | 9.5,106.1 µM (Vero), 1.6 µg/ml (Vero) | >105, / / | |||
Mycophenolic acid | DENV2 | 0.3–1.9 (Vero, Huh7) | / | ||
N-allyl-acridone (3b) | DENV1 DENV2 DENV3 DENV4 | 26.7 µM (Vero) 13.5 µM 27.1 µM 12.5 µM | >37.3 >74.1 >36.9 >80 | ||
Dihydroorotate dehydrogenase | Brequinar | DENV2 | 0.078 µM (A549) | >320 | |
NITD-982 | DENV2 | 0.005 µM (Vero) | >900 | ||
Compound 3A | / | / | / | ||
AR-12, P12-23, P12-34 | DENV2-eGFP | 0.66, 0.07, 0.05 µM (A549) | 33,297,388 | ||
P12-34 | DENV1 DENV2 DENV3 DENV4 | 0.10 µM (A549) 0.06 µM 0.09 µM 0.06 µM | 206.3 326.5 223.4 317.8 | ||
Assembly and Egress | C75 | / | / | / | |
SFV785 | / | / | / | ||
Lovastatin | DENV2 | 38.4 µM (Vero) | 1.4 | ||
Nordihydroguaiaretic Acid | / | / | / | ||
Dasatinib | / | / | / | ||
Sunitinib | DENV1 DENV2 DENV3 DENV4 | 0.6 µM (BHK-21) 0.51 µM 0.3 µM 0.23 µM | >16.6 22.6 >33 >43 | ||
Erlotinib | DENV1 DENV2 DENV3 DENV4 | 1.9 µM 2.5 µM 1.3 µM 3.9 µM | >10 >8 >15 >5 | ||
Castanospermine | DENV2 | 85.7 µM (Huh7) −1 µM (BHK-21) | / | ||
Hirsutine | DENV1 | 1.9 µM (A549) | >5.3 | ||
Ubiquitin proteasome pathway | Bortezomib | DENV2 DENV1-4 | 0.008 µM (BHK-21) <0.02 µM (primary monocytes) | /, >50 | |
MG132, ALLN | DENV2 | 0.4 – <10 µM (HepG2) | No tox at 0.4 and 10 µM | ||
CB-5083 NMS-873 | DENV2luc. | 0.25 µM (Huh7.5) 0.02 µM | 100 1250 | ||
Ubiquitin-activating enzyme E1 (UBE1) | UBEI-41 | / | / | / | |
Proteasome-associated deubiquitinating enzyme USP14 | IU1 | DENV2 | 40 µM (Hek293T) | 7.5 | |
