Identification of small molecule inhibitors of Ebola virus by use of a biologically contained virus system

Ebola virus disease is a severe illness with high mortality for which limited therapeutic options are available. Identifying new antiviral drugs that target viral proteins is essential for improving prevention and treatment strategies. In this study, we screened a library of 2,620 small molecules enriched for reported inhibitory activity against cellular and viral helicases to identify phenotypic inhibitors of a biologically contained virus, Ebola∆VP30 virus, in Vero cells stably expressing VP30 protein. Seven compounds significantly reduced virus titers at least 100-fold with minimal cytotoxicity and demonstrated low IC₅₀ values. Two of these compounds completely inhibited EbolaΔVP30 virus infection, interfering with either virus entry or replication. Although these preliminary screening hits require further optimization and in vivo validation, their identification opens new avenues for anti-Ebola virus drug discovery.