TABLE 1.
Compounds targeting CHIKV entry and egressa
| Compoundb | Viral target | Resistance mutation(s) |
In vitro efficacy |
In vivo efficacy |
Reference(s) | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| CHIKV strain (genotype)c | EC50 (μM) or other readoutd | CC50 (μM) | Cell line | CHIKV strain (genotype) | Efficacy | Mouse model | ||||
| Obatoclax (R) | E1 | L369I (SFV) | LR2006 OPY1 (ECSA genotype) | 0.03 ± 0.01 | 20.1 ± 4.8 | BHK-21 | — | — | — | 21 |
| Arbidol | E2 | G82R | LR2006 OPY1 (ECSA) | 12.2 ± 2.2 | 376 | MRC5 | — | — | — | 22 |
| Suramin (R) | E2 | N5R, H18Q | CHIKV-LS3 | 79 ± 11.6 | >1,000 | VeroE6 | 0611aTw, 0810bTw, 0706aTw (Asian) | Reduced viral load, foot swelling, and histopathologic lesions | C57BL/6 | 25, 28, 29 |
| Picolinic acid | C | — | DRDE-07 (ECSA) | 60% inhibition with 2 mM dose | n.s. | Vero | — | — | — | 30 |
| Amantadine | 6k | — | S27 (ECSA) | 29.5 | >200 | Vero | — | — | — | 32 |
| Chloroquine (R) | — | — | DRDE-06 (ECSA) | 7.0 ± 1.5 | >260 | Vero | — | — | — | 38 |
| Doxycycline (R) | — | — | n.s. (ECSA) | 10.95 ± 2.12 | >100 | Vero | 061573 (ECSA) | No significant reduction in viral titer or pathology | ICR | 39 |
| Curcumin | — | — | LR06-049 (ECSA) | 3.89 | 11.6 | HeLa | — | — | — | 41 |
| Niclosamide | — | — | S27 (ECSA) | 0.95 ± 0.22 | >20 | BHK-21 | — | — | — | 42 |
| Nitazoxanide | — | — | S27 (ECSA) | 2.96 ± 0.18 | >25 | BHK-21 | — | — | — | 42 |
| Apigenin | — | — | LR2006 OPY1 (ECSA) | 70.8 | >200 | BHK-21 | — | — | — | 43 |
| FL3 | — | — | Clinical isolate (ECSA) | 0.0224 | 0.119 | HEK-293T | — | — | — | 44 |
CC50, 50% cytotoxic concentration; EC50, 50% effective concentration; n.s., not specified; —, not determined/not done (in vivo studies); R, repurposed compound. The numbering of mutations that provide resistance is based on the CHIKV genome sequence of the strain indicated in the table, unless indicated otherwise.
If the study described a family/class of compounds with antiviral activity, only the antiviral activity of the most potent and/or the most representative compound is reported.
Only compounds for which the antiviral activity was tested using infectious CHIKV are included; compounds identified using only replicon/surrogate systems for which confirmatory experiments with infectious CHIKV were lacking are excluded.
When a compound showed activity in multiple cell lines and against multiple CHIKV strains, the value corresponding to the best activity (with corresponding cell line) is reported.