Table 1.
Drugs Advanced to Synergy Tests Against Ebola Virus Infection of Huh7 Cells
Druga | Anti-EBOV Activity Detected, by Testb | Stage Blocked | Step Blockedc | Status | Clinical Used |
---|---|---|---|---|---|
3-Deazaneplanocin A | 1, 2 | Postentry | RNA synthesis | Preclinical study | NA |
Amodiaquine e | 2 | Entry | Acidification | FDA approved | Antimalarial |
Apilimod | 1, 2 | Entry | Traffic | Phase 2 study in US | NA |
Aripiprazole | 2 | Entry | Internalizationf | FDA approved | Psychosis |
Azithromycin e | No | Entry | Fusionf | FDA approved | Antibacterial |
Bepridil e | 2 | Entry | Fusion | FDA approvedg | Hypertension |
Clomiphene | 1, 2 | Entry | Fusion | FDA approved | Female infertility |
Colchicine | 1, 2 | Entry | Traffic | FDA approved | Gout |
Favipiravir | No | Postentry | RNA synthesis | JMHLW approved, phase 3 study in US | Antiinfluenza |
Mycophenolate | 1, 2 | Postentry | RNA Synthesis | FDA approved | Immunosuppression |
Omacetaxine | 1, 2 | Postentry | Protein synthesis | FDA approved | Hematologic tumors |
Piperacetazine | 2 | Entry | Acidificationf | FDA approvedg | Schizophrenia |
Sertraline | 1 | Entry | Fusion | FDA approved | Depression |
Sunitinib | 1, 2 | Entry | Traffich | FDA approved | Renal and GI tumors |
Toremifene | 1, 2 | Entry | Fusion | FDA approved | Breast cancer |
Abbreviations: FDA, Food and Drug Administration; GI, gastrointestinal; JMHLW, Japanese Ministry of Health, Labor and Welfare; US, United States.
aDrugs tested in combinations against Ebola virus in matrix synergy tests (Supplementary Data Set 2), unless otherwise indicated.
bDrug activity against Ebola virus in single-agent test 1 (with frozen chemical plates) or 2 (with freshly plated drugs). Positive drug activity in test 1 or 2 is indicated by test number.
c“Acidification” denotes endosome acidification, “traffic” denotes traffic to late endosomes, “internalization” denotes internalization from the cell surface, and ”fusion“ denotes fusion with late endosome.
dInformation on clinical use was obtained from DrugBank (available at: https://www.drugbank.ca/).
eDrugs tested in combinations against Ebola virus in subsequent tests (Supplementary Data Set 3).
fE. A. Nelson and J. M. White, unpublished data.
gCurrently discontinued.
hAction of sunitinib against EBOV is postulated to be similar to action against dengue virus [33].