Table 2.
Therapeutics for EBOV infection
| Molecule | Mechanism of Action | Development Phase | Reference |
|---|---|---|---|
| Favipiravir | A nucleotide analog that inhibits RNA polymerase. | Has been shown to protect mice against EBOV. Administered to one EBOV infected patient who survived. Currently in Phase II trial. |
63 |
| PMOs AVI-6002 (AVI-7537 and AVI-7539) AVI-6003 (AVI-7287 and AVI-7288) |
AVI 7537 targets EBOV VP24; AVI-7539 targets EBOV VP35 AVI-7287 targets MARV VP24; AVI-7288 targets MARV NP |
AVI-6002 has been shown to provide partial protection of rhesus macaques against EBOV. AVI-7537 confers sole protection observed. AVI-6003 has been shown to completely protect cynomolgus macaques from MARV infection. Completed Phase I clinical trial. |
71 |
| ZMapp | Monoclonal cocktail of antibodies against different epitopes of EBOV-GP. | Has been shown to completely protect cynomologus macaques. Protected 5/7 patients infected with EBOV. Currently in Phase I clinical trial. | 83,85 |
| BCX4430 | An adenosine analog that inhibits RNA transcription. | Shown to protect cynomolgus macaques against Marburg virus. In Phase I clinical trial. |
66 |
| Brincidofovir | Inhibits DNA synthesis. Mechanism against RNA viruses is unknown. | Shows efficacy against EBOV in vitro. Protected 1 of 2 US patients infected with EBOV. Withdrawn from Phase II clinical trial | 69,68 |
| TKM-Ebola | Treatment with SNALP carrying siRNAs against EBOV L polymerase, VP24, and VP35. | Protected macaques following EBOV challenge. Phase I trial were halted. FDA expanded access to TKM-Ebola on an emergency basis. | 74–75 |
| rhAPC | Anticoagulant | Recombinant human activated protein C is an anticoagulant that prolongs survival time and provides partial protection in nonhuman primates. | 59b |
| rNAPc2 | Anticoagulant | Recombinant nematode anticoagulant protein c2 prolongs survival time and provides partial protection in nonhuman primates. | 59a |
| IFNβ | Interferon | Prolongs mean time-to-death in rhesus macaques infected with EBOV. May be possible adjunctive post-exposure therapy | 62 |
| Chloroquine | The antiviral mechanism is unknown. | FDA approved as an antimalarial agent. Through a screening study evaluating 1012 FDA-approved drugs, chloroquine was found to possess in vitro activity against EBOV. Found to protect mice against EBOV infection in vivo. | 87 |
| Selective estrogen receptor modulators: clomiphene and toremifene | Inhibits EBOV entry. | Clomiphene and toremifene inhibit EBOV infection in vitro and show partial protection in mice challenged with mouse adapted EBOV. | 88 |
| FGI compounds: FGI-103, FGI-104, FGI-106 |
FGI compounds are broad-spectrum viral inhibitors. Antiviral mechanism against EBOV is unknown. |
Exhibited efficacy against EBOV in vitro and in mouse models. | 89,90,91 |
| SAH hydrolase inhibitor Deazaneplanocin A | Targets SAH hydrolase, indirectly resulting in reduced methylation of 5’ cap of viral messenger RNA. May also increase IFNα production | Early dose protected mice against EBOV challenge. | 92 |
| Glucosidase inhibitors: CM-10-18, IHVR11029, IHVR17028 and IHVR19029 | Glucosidase inhibitors inhibit Endoplasmic reticulum α-glucosidases I and II and prevent maturation of viral glycosylated envelope and, inhibiting viral entry. | CM-10-18, IHVR11029, IHVR17028 and IHVR19029 has been shown to suppress mortality of MARV and EBOV infection in mice. | 93 |
| Antioxidant NSC62914 | Acts as a scavenger of reactive oxygen species and upregulates oxidative stress-induced genes. | Exhibits anti-filovirus activity in vitro and in vivo in mice infected with EBOV or Marburg virus. | 94 |
| HSPA5 inhibitors | Targets HSPA5 chaperone (EBOV-associated host factor). | PMOs targeting HSPA5 reduced viral replication and protected mice against lethal EBOV infection. | 95 |
| SAH hydrolase inhibitor Neplanocin A, 3- | Targets SAH hydrolase, indirectly resulting in reduced methylation of 5’ cap of viral messenger RNA | Efficacy of Neplanocin A against EBOV has been shown in vitro. | 96,97 |
| Benzylpiperazine adamantine diamides | Inhibits EBOV entry via cholesterol transporter Niemann-Pick C1 in vitro | Shown to inhibit EBOV entry in vitro. | 98,99 |
| LJ-001 | A rhodamine derivative, which prevents fusion of viral and cellular membranes and prevents viral entry. | Shown to inhibit EBOV entry in vitro. | 100 |
| CMLDBU3402 | Broad-spectrum antiviral Inhibits EBOV RNA transcription | Shown to inhibit EBOV entry in vitro | 101 |
| Ion channel blockers: amiodarone, dronedarone, verapamil |
Inhibit EBOV entry | Shown to inhibit EBOV entry in vitro. | 102 |
| Heme oxygenase-1 (HO-1) | Inhibit EBOV replication. Mechanism unknown | HO-1 induction significantly suppressed EBOV replication in vitro. | 103 |
| Lamivudine | Cytosine analog approved for treatment of HIV and hepatitis B virus. Unknown mechanism against EBOV | Not yet evaluated in context of EBOV. Studies against EBOV in vitro are currently being conducted | 104 |
| duY11 | A rigid amphipathic fusion inhibitor (RAFI) targets entry of enveloped viruses and may potentially inhibit entry of EBOV | Not yet assessed in in vitro or in vivo studies against EBOV | 105 |
| Inhibitors of cathepsin L cleavage | Prevention of cathepsin L cleavage of viral glycoproteins may inhibit EBOV entry. | Not yet assessed in in vitro or in vivo studies | 106 |
| Statins | Anti-inflammatory | No in vitro or in vivo studies in efficacy against Ebola. However, may be used to treat viral sepsis during EBOV infection. FDA approved | 107 |