Table 2 Post-entry virus-directed DENV antivirals
Stage | Compound | DENV serotype | IC50/ (90) | SI:CC50/IC50 | Reference |
|---|---|---|---|---|---|
5′ and 3′ stem loop | Peptide-conjugated phosphorodiamidate morpholino oligomers | DENV2 | 1 µM (BHK) | 25 | |
NS2B-NS3 protease cleavage | Benzyl ethers of 4-hydroxyphenylglycine (compound 104) | DENV2 | 3.4 µM (Huh-7) | >25 | |
Boronic acids analogues (compound 7) | Anti-NS2B-NS3 | 18 µM | >5 | ||
Thiazolidinone-peptide hybrid 10a | DENV2luc. | 16.7 µM (Huh-7) | >3 | ||
N-sulfonyl-peptide-hybrids | Anti-NS2B-NS3 | 0.078 µM | / | ||
Phenylalanine analogues (Compound 45a) | Anti-NS2B-NS3 | 0.26 µM | / | ||
Diaryl(thio)ethers (Compound 1–6, 8) | DENV2 | 0.1–3.5 µM (Vero) | ±10 | ||
Protegrin-1 | Anti-NS2B-NS3 | 11.7 µM | / | ||
Retrocyclin-1 | Anti-NS2B-NS3 | 21.4 µM | / | ||
Flavonoids | Anti-NS2B-NS3 | 21 µM | / | ||
ARDP0006 | DENV2 | 4.2 µM (LLC-MK2) | 16.6 | ||
BP13944 BP2109 | DENV2luc. | 1.03 µM (BHK-21) 0.17 µM | 70 172 | ||
Tolcapone (Compound F) | DENV2 | 2.03 µM (BHK-21) | 14.36 | ||
166347 | DENV1 (anti-NS2B-NS3) DENV2 DENV3 DENV4 | 3 µM 5 µM 5 µM 11 µM | / | ||
SK-12 | DENV1 DENV2 DENV3 DENV4 | 0.97 µM (Vero) 0.98 µM 2.43 µM 0.74 µM | 69 69 28 91 | ||
Policresulen | DENV2luc. | 4.99 µg/ml (BHK-21) | 92 | ||
Palmatine | DENV2 | 26.4 µM (Vero) | 39 | ||
Nelfinavir | DENV2 | 3.5 µM (Vero-B) | 4.6 | ||
ABT263, ABT737, AT101, and TW37 | Anti-NS2B-NS3 | 0.86, 1.15, 0.81, and 0.89 µM | / | ||
NS3 helicase activity | Suramin | Molecular beacon Helicase assay | 0.4 µM | / | |
ST-610 | DENV1 DENV2 DENV3 DENV4 | 0.24 µM (Vero) 0.27 µM 0.26 µM 0.20 µM | >370 | ||
Ivermectin | DENV2 | 0.7 µM (Vero) | 5.42 | ||
Compound 24 (benzothiazole) Compound 25 (pyrrolone) | DENV2luc. | 7.1 µM (BHK-21) 36 µM | 17 4.5 | ||
NS5 methyltransferase activity | AT-752, AT-281 | DENV1luc. DENV2luc. DENV3luc. DENV4luc. | 0.57 µM (Huh7) 0.30 µM 0.75 µM 0.57 µM | >298 >566 >226 >298 | |
Azidothymidine based thiazoles (compound 11i) | DENV2luc. | 7.5 µM (BHK) | 2.9 | ||
NSC 12155 | DENV2 | 7.0 µM (A549) | 13.7 | ||
Sinefungin | DENV MTase activity | 0.03–0.04 µM | / | ||
NS5 guanylyltransferase | BG-323 | DENV2luc. | 30.8 µM (BHK) | 6.0 | |
NS5 polymerase activity | Balapiravir (R1479) | DENV1-4 | 1.9–11 µM (Huh7) | / | |
NITD008 | DENV2 | 0.64 µM (Vero) 1.64 µM (Huh7) | >156 >61 | ||
AT-752, AT-281 | DENV1luc. DENV2luc. DENV3luc. DENV4luc. | 0.57 µM (Huh7) 0.30 µM 0.75 µM 0.57 µM | >298 >566 >226 >298 | ||
7-deaza-2-C-methyl-adenosine | DENV2 | 15 µM (Vero) | >21 | ||
Compound 29 (acyl-sulfonamide derivatives) | DENV2luc. | 1.9 µM (Huh7) | >26 | ||
Compound 27 (biphenyl acetic acid) | DENV1 DENV2 DENV3 DENV4 | 1.8 µM (A549) 2.3 µM 1.8 µM 1.8 µM | >27 >21 >27 >27 | ||
NITD-434 NITD-640 | DENV2 | 31.2 µM 10.7 µM | >1.6 >4.7 | ||
NS3-NS4B complex formation | JNJ-A07 JNJ-1802 | DENV1-4 DENV2 | ≤0.006 µM (Vero) 0.000059 µM (Vero) | 130.000 44.000 | |
NS4B | NITD-681 | DENV1 DENV2 DENV3 DENV4 | 1.5 µM (BHK-21) 1.6 µM 1.6 µM 4.1 µM | >9.8 | |
NITD-688 | DENV1-4 DENV2 | 0.008–0.038 µM (A549) 0.007 µM (Huh7) | ≤732 4171 | ||
Lycorine | DENV1-2 | / | / | ||
Spiropyrazolopyridone and derivatives (1a) | DENV2 | 0.012 µM (HepG2) | >833 | ||
SDM25N | DENV2luc. | 1.9 µM (Hela) | >5 | ||
AM404 | DENV2luc. | 3.6 µM (Hela) | >7 |
