•T-705 suppressed replication of Zaire EBOV by 4 log units in cell culture. •Mice lacking the type I interferon receptor (IFNAR−/−) were used as in vivo model. •In this model, T-705 administration prevented a lethal outcome. •Treatment was effective even if initiated at day 6 post infection. Outbreaks of Ebola hemorrhagic fever in sub-Saharan Africa are associated with case fatality rates of up to