Table 1.
Potential antiviral candidates against EBOV infection.
| Category | Drug(s) | Stage | IC50 (In Vitro) | Ref. |
|---|---|---|---|---|
| VP35 inhibitors | VP35 PMO and P-PMO | In vivo | 0.9–1.25 μM (P-PMO; wtEBOV) | [22] |
| Myricetin | In vitro | 2.7 μg/mL (enzymatic) | [23] | |
| MCCB4 | In vitro | 4.8 μM (EBOV minigenome) | [24] | |
| Anti-VP35 scFvs | In vitro | N.D. | [25] | |
| VP40 inhibitors | Anti-VP40 scFv | In vitro | N.D. | [26] |
| Quinoxaline-based inhibitors | In vitro | N.D. | [27] | |
| Sorbitol, mannitol, galactitol | In silico | N.D. | [28] | |
| Pyrimidinediones class molecules | In silico | N.D. | [29] | |
| GP inhibitors | mAb114 | Licensed (Ebanga™) | 0.09 μg/mL (wtEBOV) | [30] |
| REGN-EB3 (REGN3470, REGN3471, REGN3479) | Licensed (Inmazeb™) | 0.39 nM (EBOVpp) | [31] | |
| ZMappTM (c13C6, c2G4, c4G7) | Clinical trial | N.D. | [32] | |
| MIL77E (MIL77-1, MIL77-3) | In vivo | 1–10, 10–100 μg/mL (EBOV-GFP) | [33] | |
| ZMAb (m1H3, m2G4, m4G7) | In vivo | 18.75, 4.325, 0.678125 μg/mL (EBOVpp) | [34] | |
| MB-003 (c13C6, h13F6, c6D8) | In vivo | N.D. | [35,36,37,38] | |
| KZ52 | In vivo | 0.3–0.9 μg/mL (wtEBOV) | [39] | |
| Q206, Q314, Q411 | In vivo | 0.36, 0.78, 0.43 μg/mL (EBOVpp); 7.08, 42.96, 15.24 μg/mL (EBOV-GFP) | [40] | |
| 2G1, 5E1, 5E9 | In vivo | 2.80, 11.13, 4.19 μg/mL (EBOV-GFP) | [41] | |
| 6D6 | In vivo | 0.05–0.12 μg/mL (EBOVpp) | [42] | |
| m8C4 | In vivo | 1.5 μg/mL (EBOVpp) | [43] | |
| Bis-mAbs | In vivo | 1.5–6.4 nM (EBOVpp); 0.5–1.1 nM (wtEBOV) | [44] | |
| CA45 | In vivo | 3.0–4.63 nM (EBOVpp); 28.3 nM (live virus) | [45] | |
| FVM04 | In vivo | 0.8–3.4 μg/mL (EBOVpp) | [46] | |
| 040, 66-3-9C, 6662, 6541 | In vivo | 0.1–10 μg/mL (EBOVpp) | [47] | |
| MBP134AF | In vivo | 0.1–1 nM (EBOVpp) | [48] | |
| rEBOV-520, rEBOV-548 | In vivo | 0.1–1, 1–10 μg/mL (EBOV-GFP) | [49] | |
| EBOV/SUDV pAb | In vivo | N.D. | [50] | |
| F(ab’)2 | In vivo | 1.4–1.7 μg/mL (EBOV-GFP) | [51] | |
| rhMBL | In vivo | N.D. | [52] | |
| Clomiphene | In vivo | 0.755–2.42 μM (EBOV-GFP); 3.83–11.1 μM (wtEBOV) | [53] | |
| Toremifene | In vivo | 0.0255–0.162 μM (EBOV-GFP); 0.973–1.73 μM (wtEBOV) | [53] | |
| Bepridil | In vivo | 3.21–5.08 μM (EBOV-GFP); 4.54 μM (wt EBOV) | [54] | |
| Sertraline | In vivo | 1.44–3.13 μM (EBOV-GFP); 3.73–8.62 μM (wtEBOV) | [54] | |
| HP-HSA | In vitro | 0.068 μM (EBOVpp) | [55] | |
| PPCM | In vitro | N.D. | [56] | |
| Sclareol, sclareolide | In vitro | 2.4, 8.0 μM (EBOVpp) | [57] | |
| Compound 7 | In vitro | 10 μM (EBOV-GFP) | [58] | |
| Compound 118, compound 118a | In vitro | 3.1, 0.05 μM (EBOVpp) | [59] | |
| 11 compounds from ZINC database | In vitro | 1.79–36.66 μM (EBOVpp) | [60] | |
| VP30 inhibitors | SRPK1/SRPK2 inhibitor (SRPIN340) | In vitro | N.D. | [61] |
| PP2A-B56 inhibitor | In vitro | N.D. | [62] | |
| PP1α inhibitor (C31) | In vitro | N.D. | [63] | |
| VP24 inhibitors | VP24 PMOs | In vivo | 8–11 nM (enzymatic) | [64] |
| Gossypetin, taxifolin, tricetin | In vitro | N.D. | [65,66] | |
| Quercetin | In vitro | 7.4 μM (enzymatic) | [66] | |
| Cycloartocarpin | In silico | N.D. | [67] | |
| ZINC000095486070, ZINC000003594643, ZINC000095486008, Sarcophine | In silico | N.D. | [68] | |
| Polymerase inhibitors | Brincidofovir | Clinical trial | 120 nM–1.3 µM | [69] |
| Favipiravir | Clinical trial | 67 μM (wtEBOV) | [70] | |
| Galidesivir | Clinical trial | 11.8 μM (wtEBOV) | [71] | |
| Remdesivir | Clinical trial | 0.06–0.14 μM (EBOV-GFP or wtEBOV) | [72] | |
| SNALPs (L) | In vivo | N.D. | [73] | |
| Lamivudine, zidovudine | In vitro | >320 µM (wtEBOV) | [74] | |
| Pairs of approved nucleotide analogues | In silico | N.D. | [75] | |
| Host-targeting inhibitors—Viral entry | Amiodarone | Clinical trial | 2.02 μM (EBOVpp); 0.25 μg/mL (wtEBOV) | [76] |
| Amiodarone | Clinical trial | 5.6 μM (EBOVpp) | [77] | |
| Amiodarone | Clinical trial | 0.81 μM (EBOVpp); 7.6 μM (EBOV-GFP) | [78] | |
| Amiodarone | Clinical trial | 5.5–15.9 μM (wtEBOV) | [79] | |
| AMPK inhibitor (Compound C) | In vitro | ∼6 μM (EBOVpp) | [80] | |
| MAPK inhibitors | In vitro | 2.67–8.26 μM (EBOV-GFP) | [81] | |
| GlcNAc-1-phosphotransferase inhibitor (PF-429242) | In vitro | 0.80 μM (EBOVpp); 0.95 μM (EBOV-ZsG) | [82] | |
| Emetine | In vitro | 10.2 μM (EBOV VLP); 16.9 nM (EBOV-GFP) | [83] | |
| Dronedarone, verapamil | In vitro | N.D. | [76] | |
| GPCR antagonists | In vitro | 3.7–19.4 μM (EBOV-GFP) | [84] | |
| SERMs | In vitro | N.D. | [85] | |
| ErbB kinase inhibitor (BIBX 1382) | In vitro | 1.1 μM (EBOV-GFP) | [86] | |
| Host-targeting inhibitors—Viral replication | HspA5 inhibitors | In vivo | 50–60 μM (EGCG; live virus) | [87] |
| Hsp90 inhibitors | In vitro | 43.8–394.5 nM (EBOV-GFP) | [88] | |
| eIF4A inhibitor (silvestrol) | In vitro | ∼0.8 nM (live virus) | [89] | |
| Emetine, cycloheximide, mycophenolic acid | In vitro | 1.474, 0.608, 0.316 μM (EBOV-GFP) | [90] | |
| Host-targeting inhibitors—Antiviral immunity | SAH inhibitor (Ca-c3 Ado) | In vivo | 30 μM (wtEBOV) | [91] |
| SAH inhibitor (c3-Npc A) | In vivo | 2 μM (wtEBOV) | [91] | |
| IFNs | In vivo | <10–5102 U/mL (wtEBOV) | [92] | |
| Nitazoxanide | In vitro | N.D. | [93] | |
| Host-targeting inhibitors—Viral egress | TSG101 inhibitor (FGI-104) | In vivo | 10 μM (EBOV-GFP) | [94] |
| Host-targeting inhibitors—Anticoagulant | rNAPc2 | In vivo | N.D. | [95] |
| rhAPC | In vivo | N.D. | [96] | |
| Combination Treatments | PMOs (VP24, VP35, L) | In vivo | N.D. | [97] |
| PMOplus AVI-6002 (VP24, VP35, L) | In vivo | N.D. | [98] | |
| Ad-IFN-α + Ad-CAGoptZGP | In vivo | N.D. | [99] | |
| Ad-IFN-α + ZMAb | In vivo | N.D. | [100] | |
| anti-GP + anti-VP40 | In vitro | N.D. | [101] | |
| Combinations of IFNs and nucleoside analogs | In vitro | N.D. | [102] | |
| Toremifene + mefloquine + posaconazole, toremifene + clarithromycin + posaconazole | In vitro | 1.08, 0.97 μM (Ebola VLP) | [103] | |
| Aripiprazole + piperacetazine, sertraline + toremifene, sertraline + bepridil, amodiaquine + clomiphene | In vitro | N.D. | [104] | |
| Digitoxin + tetrandrine, digitoxin + tamoxifen, digitoxin + fluvastatin, tamoxifen + fluvastatin | In vitro | N.D. | [105] | |
| Inhibitors with unknown target(s) | 17 compounds from MLSMR library | In vitro | 1.6–25.6 μM (EBOV-GFP) | [106] |
| Compound 8a and derivatives | In vitro | 2.5–30 μM (EBOVpp) | [107] | |
| Azithromycin | In vivo | 1.3 μM (EBOVpp); 5.1 μM (EBOV-GFP) | [78] | |
| Teicoplanin | In vivo | 2.38 μM (EBOVpp) | [108] | |
| Teicoplanin | In vivo | 7.28 μM (EBOV-GFP) | [54] | |
| Chloroquine | In vivo | 4.7 μM (EBOVpp); 16 μM (EBOV-GFP) | [78] | |
| Chloroquine | In vivo | 3.319 μM (EBOVpp) | [109] | |
| Chloroquine | In vivo | 15.3 μM (EBOV VLP) | [110] | |
| Chloroquine | In vivo | 4.7 μM (EBOVpp); 16 μM (EBOV-GFP) | [78] | |
| Chloroquine | In vivo | 1.77 μg/mL (EBOV-GFP) | [111] | |
| Quercetin 3-β-O-D-glucoside | In vivo | 5.3 μM (EBOV-GFP) | [112] | |
| FDA-approved compounds | In vitro | <25 μM (EBOV VLP) | [110] |
AMPK, AMP-activated protein kinase; EBOV, Ebola virus; EBOV-GFP, EBOV expressing green fluorescence protein; EBOVpp, EBOV pseudoparticle; GlcNAc, N-acetylglucosamine; GPCR, G protein-coupled receptor; HP-HSA, 3-hydroxyphthalic anhydride-modified human serum albumin; Hsp, heat shock protein; IC50, 50% inhibitory concentration; IFN, interferon; mAb, monoclonal antibody; MAPK, mitogen-activated protein kinase; N.D., not determined; pAb, polyclonal antibody; PMO, phosphorodiamidate morpholino oligomers; P-PMO, PMO conjugated to cell-penetrating peptide; PPCM, polyphenylene carboxymethylene; PP1, protein phosphatase 1; PP2A-B56, protein phosphatase 2A-B56; rhAPC, recombinant human activated protein C; rhMBL, recombinant human mannose-binding lectin; rNAPc2, recombinant nematode anticoagulant protein c2; SAH, S-adenosyl-l-homocysteine hydrolase; scFv, single-chain variable fragment; SERM, selective estrogen receptor modulator; SNALP, stable nucleic acid-lipid particle; SRPK, serine-arginine protein kinase; SUDV, Sudan virus; VLP, virus-like particle; VP, viral protein; wtEBOV, wild-type EBOV.