Table 2.
Potential ZIKV Therapeutics
| Therapeutic | In vivo activity against ZIKV or other flaviviruses |
In vitro data (Effective concentration, specificity index, cell type) |
Safety/ Use in pregnant women | Availability/ Feasibility |
|---|---|---|---|---|
| Amodiaquine | unknown | DENV EC90=2.7uM, SI ~10 in BHK-21 cells | unlikely teratogenic; occasional agranulocytosis, neutropenia, hepatotoxicity SAE in long-term use in some CYP2C8 gene variants | common antimalarial; possible benefit against EBOV |
| Chloroquine | DENV: no decrease in adult viremia | DENV: 0.5 ug/ml in Vero cells. No effect in C6/36 cells | Safe | common antimalarial |
| Ribavirin | DENV: not effective in NHPs; YF: increased hamster survival | ZIKV: EC50 = 140 ug/ml Vero, SI >55; DENV: EC50 = 20 ug/ml Vero, SI >400; YF: EC50=42ug/ml Vero, SI = 174 | Teratogenic | readily available; broad use antiviral |
| Interferon a | JEV: no effect in infants | JEV: EC50=4.8 IU/ml Vero; ZIKV: EC50= 34 IU/ml Vero | efficacy against hepatitis viruses | |
| BCX4430 (Biocryst, USA) | YF: increased hamster survival | YF: EC50=8.3 ug/ml Vero SI = ~5; DENV: EC50=13ug/ml; WNV:EC50=16ug/ml | Phase I safety completed, no information on teratogenicity | |
| GS-5734 (Gilead, USA) | EBOV: reduced mortality and pathology in infected NHPs | EBOV: inhibits viral replication in multiple human cell types; ZIKV: under investigation | Phase I safety completed, no information on teratogenicity | |
| NITD008 | DENV2: decreased viremia/mortality in mice | DENV: EC50 = 3uM; WNV: EC50=5 uM; YF: EC50=3uM | no human safety data | likely long time to human safety data |
| Monoclonal antibodies | ZIKV: complete protection in mice | likely safe but possible antibody-mediated pathology | cost and other considerations limit widespread use | |
| Emricasan | Protected cultured human neural cells from ZIKV-induced cell death | Phase II for liver protection from HCV showed no SAE; teratogenicity unknown | being studied for protection from hepatitis C virus (HCV) liver pathology | |
| Niclosamide | Inhibited JEV replication in BHK21 cells; inhibited ZIKV replication in human neural cells | Pregnancy category B | common teniacide | |
| PHA-690509 | Inhibited ZIKV replication in cultured human neural cells | Teratogenicity unknown | was in phase I trials for cancer therapy | |
| Duramycin | DENV, WNV: reduced infection in A549 and Vero; ZIKV: reduced infection in multiple placental cell types | hemolytic at high concentrations; teratogenicity unknown | aerosolized form in clinical trials for cystic fibrosis | |
| 3-Methyladenine (3-MA) | reduced ZIKV viral copies in infected skin fibroblast cell line | Teratogenicity unknown | authophagy inhibitor; used in chemotherapy studies | |
| EGCG | inhibited ZIKV infection of Vero cells | crosses placenta but no teratogenic effects seen in rats | controversial antiviral/dietary supplement; poor bioavailability | |
| Ranpirnase | EBOV: decreased viremia/mortality in mice | inhibited infections of Vero cells with EBOV and undisclosed cells with ZIKV | Was in phase III for mesothelioma, no information on teratogenicity | induces apoptosis in malignant cells; inhibits papillomaviruses |