Ebola viral protein 24 (VP24) inhibitor discovery by in silico fragment-based design

Ebola hemorrhagic fever (EHF) is a fatal disease caused by Ebolavirus that can potentially lead to death. The number of fatalities reached 11.000 of the 28.000 reported cases. A serious concern should be taken because neither drug nor treatment to cure this disease has been found until now. Recent studies show that viral protein 24 (VP24) is one of the non-structural protein that plays a key role in EBOV proliferation and viral life cycle. This study tried to find the potential inhibitor for EBOV VP24 through in silico experiment. About 242.520 compounds from ZINC15 In Vitro Database were obtained and screened according to the Rules of Three and pharmacological properties to get a proper lead-like fragment compounds. These compounds were docked into the active site of VP24 using MOE 2014.09 software. The potential fragment compounds were linked to generate potential inhibitor ligands. These ligands were screened earlier based on Lipinski's Rule of Five and toxicity prediction, then they were docked once again to obtain the favorable ligand. Furthermore, the dynamics simulation of best ligand, namely L833, L217, and L595, were performed to predict the ligand-enzyme complex stability. This research concludes that L595 is the best ligand. Moreover, the pharmacological and toxicity prediction also confirm that L595 can be developed as the potential inhibitor for EBOV VP24.