Identification of potential inhibitors of protein-protein interaction useful to fight against Ebola and other highly pathogenic viruses

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.

Automated summary

Despite the lack of currently licensed antiviral drugs for treating Ebola virus disease, efforts are ongoing to identify new drugs to combat EBOV. Virtual screening has led to the discovery of small organic molecules with potent inhibitory action against EBOV infection, paving the way for hit to lead optimization programs toward successful candidates.