Despite the efforts to develop new treatments against Ebola virus (EBOV) there is currently no antiviral drug licensed to treat patients with Ebola virus disease (EVD). Therefore, there is still an urgent need to find new drugs to fight against EBOV. In order to do this, a virtual screening was done on the druggable interaction between the EBOV glycoprotein (GP) and the host receptor NPC1 with a subsequent selection of compounds for further validation. This screening led to the identification of new small organic molecules with potent inhibitory action against EBOV infection using lentiviral EBOV-GP-pseudotype viruses. Moreover, some of these compounds have shown their ability to interfere with the intracellular cholesterol transport receptor NPC1 using an ELISA-based assay. These preliminary results pave the way to hit to lead optimization programs that lead to successful candidates. Display omitted •Actually there is no antiviral drugs to treat patients with Ebola virus disease.•The interaction between EBOV glycoprotein (GP) and the host receptor NPC1 is a well-known druggable target.•Virtual screening on this interaction allowed us the selection of candidates for experimental validation.•Identification of new small molecules able to inhibit EBOV infection using lentiviral EBOV-GP-pseudotype viruses.