Ebola virus (EBOV) is the causative agent of Ebola virus disease, a severe hemorrhagic fever, which is transmitted through contact with infected individuals. Once infected with EBOV, the particles enter the cell through micropinocytosis and later trafficked to the endosome. Low pH in the endosome induces a conformation change in the viral envelope glycoprotein 2 (GP2), resulting in the formation of a six-helix bundle that brings the viral and host membranes into close proximity permitting membrane fusion. Since GP2 is a homotrimeric protein, the post-fusion bundle is formed by the binding of each monomer’s C-terminal heptad repeat (CHR) to its N-terminal heptad repeat (NHR). GP2 is a class I fusion protein and due to the similarity in mechanism of viruses with class I fusion proteins, techniques used to target HIV-1 were used to identify small molecule hits with activity against GP2 that mimic the activity of the CHR. Primary and secondary virtual screens, using the program DOCK6, were performed to select 165 candidates for experimental testing to evaluate efficacy and specificity towards the EBOV. For the most potent hits, experimental results, including IC50s, and preliminary structure activity relationships will be presented.

Identification of Ebola virus inhibitors targeting viral-hots membrane fusion by glycoprotein GP2

254th National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.