Table 1.
Drug Candidates for management of ZIKV infection and its late neurologic complications.
| Drug | Proposed Mechanism of Action | In Vitro Efficacy | In Vitro Efficacy | Food and Drug Administration (FDA) Approved? | FDA Category | Refs. |
|---|---|---|---|---|---|---|
| Amodiaquine | Unknown for ZIKV (antimalarial) | Vero cell line human pluripotent stem cell-derived neural progenitors |
40 mg/kg for 7 days s.c. to adult SCID-beige mice | Discontinued | - | [80,81] |
| Azithromycin | Unknown for ZIKV (antibiotic) | U87 glial cell line | 10 mg/kg i.p. to neonatal ICR mice |
Yes | B | [82,83] |
| Chloroquine | Unknown for ZIKV (antimalarial) | human neural progenitor cells human brain microvascular endothelial cells mouse neurospheres |
50 mg/kg for 5 days + 5 mg/kg maintenance p.o. to adult AG129 mice 20 mg/kg for 6 days s.c. to pregnant BALB/c dams |
Yes | Not assigned | [84,85,86] |
| Emricasan | pan-caspase inhibitor | human neural progenitor cells human astrocytes |
N.D. | No | - | [87] |
| Favipiravir | RNA-dependent RNA polymerase inhibitor | Vero cell line induced-pluripotent neural stem cells human embryonic stem cells |
N.D. | No | - | [88,89,90,91] |
| Galidesivir (BCX4430) | RNA-dependent RNA polymerase inhibitor | Vero76 cell line Huh7 cell line RD cell line |
150 mg/kg for 8 days b.i.d. i.m.to adult AG129 mice 100 mg/kg + 25 mg/kg for 9 days b.i.d. i.m. to adult rhesus monkeys |
No | - | [92,93] |
| Infliximab | TNF-α neutralizing antibody | N.D. | 20 μg for 13 days i.p. to neonatal Swiss mice |
Yes | B | [32] |
| Memantine | NMDA receptor blocker | glial primary cells neuronal primary cells |
30 mg/kg for 4 days p.o. to adult IFN-α/βR−/− mice |
Yes | B | [94] |
| Niclosamide | endolysosomal pH neutralizer | human glioblastoma cell line (SNB-19) human astrocytes |
50 mg/kg for 2 days to chick embryos |
Yes | B | [87,95] |
| NITD008 | RNA-dependent RNA polymerase inhibitor | Vero cell line | 50 mg/kg for 5 days i.p. to adult A129 mice |
No | - | [96,97,98] |
| PHA-690509 | cyclin-dependent kinase inhibitor | human neural progenitor cells induced-pluripotent neural stem cells |
N.D. | No | - | [87] |
| Ribavirin | RNA-dependent RNA polymerase inhibitor | Vero cell line human neural progenitor cells |
15 mg for 3 days i.p. to adult STAT-1 deficient mice | Yes | X | [88,91,99] |
| Sofosbuvir | RNA-dependent RNA polymerase inhibitor | human neuroepithelial stem cell placental cell line neuroblastoma cell line human fetal-derived neuronal stem cells induced-pluripotent neural stem cells brain organoids |
33 mg/kg for 7 days p.o. to adult C57BL/6 mice 20 mg/kg for 7 days i.p. to neonatal Swiss mice |
Yes | B | [16,100,101,102,103] |
| Z2 | Direct inhibitor | Vero cell line BHK21 cell line |
Single dose of 10 mg/kg i.p. to pregnant C57BL/6 mice Single dose of 10 mg/kg i.p. to A129 and AG6 adult mice |
No | - | [104] |
B.i.d.: bis in die (twice a day); ZIKV: Zika virus; s.c.: subcutaneous; i.m. intramuscular; i.p.: intraperitoneal; p.o.: per os; N.D. no data.