Fragment-based lead compound design to inhibit Ebola VP35 through computational studies

Ebola virus (EBOV) is a virus that is classified under Filoviridae family as a pathogenic organism. On March 2016, World Health Organization (WHO) reported that 28.646 cases caused by EBOV. Thus, it is important to find the antiviral drug for this disease because it can create the epidemic around the world. EBOV VP35 is a potential drug target because it has the component of the viral RNA polymerase complex that will hamper the host interferon (IFN) production. In this research, about 6.662 fragments were obtained from ZINC15 Biogenic Database after the Rules of Three, and pharmacological properties parameters were applied. After that, these fragments were docked into the active side of EBOV VP35 using MOE 2014.09 software. The potential fragments from previous docking simulations were linked each other, resulting 91 ligands in the process. Furthermore, the docking simulation was conducted again and discovered the best three ligands that have lower Gibbs free binding energy than the standards. Moreover, the pharmacological prediction tests were also done to find the ligand with excellent molecular properties. The best three ligands from these tests were continued into molecular dynamics simulation. In the end, we conclude that the LEB 31 ligand can be the new drug candidate as EBOV VP35 inhibitor based on molecular docking, pharmacological prediction test, and molecular dynamic.