Table 3.
ZIKV Drugs targeting host proteins
| Targets | Inhibitors | IC 50 µM | ZIKV Strains | Tested Cell Lines | Animal tests | Biochemical Assays | Pregnancy Category | Reference |
|---|---|---|---|---|---|---|---|---|
| IMP dehydrogenase inhibition | Merimepodib | 0.6 | FSS13025, MR766 | Vero E6 | - | qRT-PCR. | - | [163] |
| Pyrimidine synthesis inhibitor | Cyclosporine A | unknown | MEX_1_7/2015, ZIKV DAK_41525 | Huh-7, hNSC | - | IF, Flow cytometry | C | [120] |
| Purine biosynthesis inhibitor | 6-methylmercaptopurine riboside (6MMPr) | 24.5, 20.3 | ZIKV PE243 | Vero, SH-SY5Y | - | qRT-PCR. TOA, Flow cytometry, ifa | - | [141] |
| Purine biosynthesis inhibitor | Methotrexate | 0.28 | PRVABC59, H/PAN/2016/BEI-259,634 | Vero, hNPCs | - | IFA | - | [164] |
| Nucleoside metabolic inhibitor | Palonosetron | 16.3 | ZIKVBR: (KX197192.1) | Huh-7 | - | IFA | B | [165] |
| Cholesterol metabolism inhibitor | Mevastatin | 3.42 5.05 |
MR766 PRVABC59 |
Vero 76 | ND | WB, RT-qPCR | - | [166] |
| Cholesterol metabolism inhibitor | Imipramine | - | PF-25,013-18 | HFF1, Vero | C57BL/6 N | IFA, WB, RT-QPCR, Flow cytometry | C | [167,168] |
| Cholesterol metabolism inhibitor | Benzamil | - | PRVABC59 | Vero, RPE (Retinal Pigment Epithelial) | - | qRT-PCR, IFA | B | [169] |
| Cholesterol metabolism inhibitor | Gsw4869 | - | PRVABC59 | Human fetal astrocytes, NPCs | - | TEM, WB, IFA, IHC, qRT-PCR | - | [143] |
| Cholesterol metabolism inhibitor | 7-KC | 4.064 | ZIKV SPH, ZIKV Ibh 365 | Vero, Human neurons | - | Autophagy TOA, QRT-PCR, | ||
| SREBP pathway inhibitor | Nordihydroguaiaretic acid (NDGA) | 9.1 | ZIKV PA259459 | Vero | ND | ELISA,WB, qPCR | Not approved | [145] |
| SREBP pathway inhibitor | Tetra-O-methyl nordihydroguaiaretic acid (M4N) | 5.7 | ZIKV PA259459 | Vero | ND | ELISA, WB, qPCR | - | [145] |
| caspase 3 activity inhibitor | PHA-690,509 | 1.72 | MR766, FSS13025, PRVABC59 | SNB-19, hNPCs | - | WB, IHC, TOA, caspase-3 assay, | D | [146] |
| caspase 3 activity inhibitor | Bithioniol | PRVABC59 | Vero, RAW264.7 | - | - | [147] | ||
| caspase 3 activity inhibitor | Phloretin | 22.85, 9.31 | MR766, PRVABC59 | Vero | - | IFA, WB | - | |
| Caspase inhibitor | Emricasan | 0.17, 0.13, 0.19 | MR766, PRVABC59, FSS13025 | SNB-19, hNPCs | 3D brain organoids | WB, IHC,TOA, caspase-3 assay, | - | [146] |
| Protein Metabolism inhibitor | Celgosvir | 50 | MR766, PRVABC59 | Vero 76 | ND | WB, RT-qPCR | - | [166] |
| Protein Metabolism inhibitor | Fatostatin | ≤1.2 | PA259459 | Vero | - | WB, IFA, ELISA, RT-QPCR | - | [145] |
| Protein Metabolism inhibitor | Metformin | PA259459 | Vero, BHK-21 | ND | Lipidomics, IFA, RT-QPCR | - | [170] | |
| Protein metabolism inhibitor | Cyclosporine A | 1 | MEX_1_7/2015, ZIKV DAK_41525 | Huh-7, hNSC | C57BL/6 | IFA, Flow cytometry | C | [120] |
| Endocytosis and Endosomal Fusion inhibitors(EEF) | 25-hydroxycholesterol (25HC | 0.188 | ZIKV SZ01 | Vero | A129 mice, Rhesus macaque | Plaque assay, IFA, | - | [134] |
| EEF | Arbidol | 12.09 ± 0.77, 10.57 ± 0.74 | MR66, ZIKV Paraiba-01 | Vero, PS, HBCA, UKF-NB-4 | 129 SV | IFA | - | [135,171] |
| EEF | K22 | 2.1–2.5 | PR-2015; PRVABC59 | Vero Huh-7 | - | IFA, TEM, TOA | - | [136] |
| EEF | Tenovin 1 | 0.7 | Mex2-81, FSS13025, MR766 | Jeg3, BHK-21, Vero, Human U2OS | - | RT-QPCR, TOA,IFA | - | [137] |
| EEF | Peptide EV37 | - | PRVABC59 | Huh-7, Huh 7.5.1, BHK-21, HEK293T | - | TOA, QRT-PCR, WB, Flow cytometry | - | [138] |
| EEF | Chlorpromazine | - | BeH819015, PE243/2015 | BHK-21. Huh-7, Vero E6 | C57BL/6 | IFA | - | [172,173] |
| EEF | Amodiaquine | - | ZIKV (strain PLCal_ZV) | Vero, Huh-7 | SCID-beige mice | QRT-PCR, Flow cytometry | - | [139] |
| EEF | Chloroquine | 9.82, 14.20, 12.36 | MR766, ZIKVBR | Vero, hBMECs, hNPC | A129, SJL mice | qRT-PCR,Flow cytometry, IF | - | [108] |
| Apoptosis and vATPase inhibitor | Obatoclax, Saliphenylhalamide (SaliPhe) | 0.04 0.01, 0.05 ± 0.02 | ZIKV FB-GWUH-2016, MR766, H/PF/2013 | RPE | 3D brain organoids | TDA, IFA, qRT-PCR, | - | [174] |
| Inhibits mTOR, STAT3 and NF-κB signaling pathways | Niclosamide | 0.28 | MR766, PRVABC59, FSS13025 | SNB-19, hNPCs | Chick embryos | WB, IF, TOA,caspase-3 assay, | B | [146,175,176] |
| Innate immunity and Epigenetics | GSK-126 | - | H/PF/2013 | Vero,MRC-5 | C57BL/6 J | RT-QCR, QPCR, WB, ChIP, IFA, IHC | - | [150] |
| TNF-α neutralizing antibody | Infliximab | - | - | Swiss mice | - | B | [177] | |
| NMDA receptor blocker | Memantine | HS-2015-BA-01 | hNPCs | SV129 | IHC | B | [178] | |
| Unknown | Azithromycin | SPH2015, PRVABC59, FSS13025 | HPSCs, U87 glial cell | ICR mice | - | B | [106] | |
| Unknown | Ebelsen | PRVABC59 | AG129 | IFA, IHC, WB, qRT-PCR, Histology | - | [179] |
ND – Not Done DSC- Differential Scanning Calorimetry CPE -Cytopathic Effects PRNT-Plaque Reduction Neutralization Test SPR-Surface Plasmon Resonance NMR-Nuclear Magnetic Resonance