ArticlePLoS neglected tropical diseases2016
A Rapid Screening Assay Identifies Monotherapy with Interferon-ß and Combination Therapies with Nucleoside Analogs as Effective Inhibitors of Ebola Virus.
Article in PLoS neglected tropical diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
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- TRIM25 and ZAP target the Ebola virus ribonucleoprotein complex to mediate interferon-induced restriction.PLoS pathogens · 2022Article
- Therapeutic Strategies against Ebola Virus Infection.Viruses · 2022Review
- Comparison of Zaire and Bundibugyo Ebolavirus Polymerase Complexes and Susceptibility to Antivirals through a Newly Developed Bundibugyo Minigenome System.Journal of virology · 2021Article
- Formulation, Stability, Pharmacokinetic, and Modeling Studies for Tests of Synergistic Combinations of Orally Available Approved Drugs against Ebola Virus In Vivo.Microorganisms · 2021Article
- Immunotherapeutics for Ebola Virus Disease: Hope on the Horizon.Biologics : targets & therapy · 2021Review
- Strategy, Progress, and Challenges of Drug Repurposing for Efficient Antiviral Discovery.Frontiers in pharmacology · 2021Review
- FBA reveals guanylate kinase as a potential target for antiviral therapies against SARS-CoV-2.Bioinformatics (Oxford, England) · 2020Article
- Repurposing Pyramax®, quinacrine and tilorone as treatments for Ebola virus disease.Antiviral research · 2020Article
- Overview of therapeutic drug research for COVID-19 in China.Acta pharmacologica Sinica · 2020Review
- Inhibition ofF1000Research · 2020Article
- Therapeutic strategies to target the Ebola virus life cycle.Nature reviews. Microbiology · 2019Review
- Global virus outbreaks: Interferons as 1st responders.Seminars in immunology · 2019Review
- Role of Type I Interferons on Filovirus Pathogenesis.Vaccines · 2019Review
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- High Throughput and Computational Repurposing for Neglected Diseases.Pharmaceutical research · 2018Review
- Identification of Combinations of Approved Drugs With Synergistic Activity Against Ebola Virus in Cell Cultures.The Journal of infectious diseases · 2018Article
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
To date there are no approved antiviral drugs for the treatment of Ebola virus disease (EVD). While a number of candidate drugs have shown limited efficacy in vitro and/or in non-human primate studies, differences in experimental methodologies make it difficult to compare their therapeutic effectiveness. Using an in vitro model of Ebola Zaire replication with transcription-competent virus like particles (trVLPs), requiring only level 2 biosafety containment, we compared the activities of the type I interferons (IFNs) IFN-α and IFN-ß, a panel of viral polymerase inhibitors (lamivudine (3TC), zidovudine (AZT) tenofovir (TFV), favipiravir (FPV), the active metabolite of brincidofovir, cidofovir (CDF)), and the estrogen receptor modulator, toremifene (TOR), in inhibiting viral replication in dose-response and time course studies. We also tested 28 two- and 56 three-drug combinations against Ebola replication. IFN-α and IFN-ß inhibited viral replication 24 hours post-infection (IC50 0.038μM and 0.016μM, respectively). 3TC, AZT and TFV inhibited Ebola replication when used alone (50-62%) or in combination (87%). They exhibited lower IC50 (0.98-6.2μM) compared with FPV (36.8μM), when administered 24 hours post-infection. Unexpectedly, CDF had a narrow therapeutic window (6.25-25μM). When dosed >50μM, CDF treatment enhanced viral infection. IFN-ß exhibited strong synergy with 3TC (97.3% inhibition) or in triple combination with 3TC and AZT (95.8% inhibition). This study demonstrates that IFNs and viral polymerase inhibitors may have utility in EVD. We identified several 2 and 3 drug combinations with strong anti-Ebola activity, confirmed in studies using fully infectious ZEBOV, providing a rationale for testing combination therapies in animal models of lethal Ebola challenge. These studies open up new possibilities for novel therapeutic options, in particular combination therapies, which could prevent and treat Ebola infection and potentially reduce drug resistance.
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