ID: 68: IFN-β treatment for Ebola virus disease: Bench to bedside

Abstract

To date there are no approved vaccines or antiviral drugs for the treatment of Ebola virus disease (EVD). While a number of candidate drugs have shown limited efficacy in preclinical 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, we compared the antiviral activities of 8 different candidate antivirals from 3 drug classes: IFN-α and IFN-s, 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). We also tested 28 two- and 56 three-drug combinations against Ebola replication. IFN-α and IFN-β inhibited viral replication 24 h post-infection (IC50 0.038 μM and 0.016 μM, respectively). 3TC, AZT and TFV inhibited Ebola replication when used alone (50–62%) or in combination (87%). They exhibited lower IC50 (0.98–6.2 μM) compared with FPV (36.8 μM), when administered 24 h post-infection. CDF had a narrow therapeutic window (6.25–25 μM). When dosed >50 μM, CDF treatment enhanced viral infection. IFN- β exhibited strong synergy with 3TC (97.9% inhibition) or in triple combination with 3TC and AZT (98.5% inhibition). Our data indicate that IFN-β is a potent inhibitor of Ebola virus, superior to the antivirals we tested, contributing to the decision to conduct a clinical trial of IFN-β treatment for Ebola virus disease in Coyah, Guinea. Results from the trial, including effects of IFN treatment on viremia, disease symptoms and survival will be presented.