TY - JOUR
T1 - Ebola viral protein 24 (VP24) inhibitor discovery by in silico fragment-based design
AU - Tambunan, Usman Sumo Friend
AU - Siregar, Syafrida
AU - Toepak, Erwin Prasetya
N1 - Funding Information:
Directorate of Research and Community Engagement of Universitas Indonesia (DRPM UI) has been donating the research and publication of this article by Hibah Publikasi International Terindeks Untuk Tugas Akhir Mahasiswa No: 693/UN2.R3.1/HKP.05.00/2017. USFT designed the study and supervised this research, while SS and EPT were performed the experimental details. Mr. Mochammad Arfin Fardiansyah Nasution for helping us to proofread this paper.
Publisher Copyright:
© 2018, Int. J. of GEOMATE.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - Ebolavirus
KW - Fragment-based
KW - Molecular docking
KW - Toxicity prediction
KW - Viral protein 24
UR - http://www.scopus.com/inward/record.url?scp=85048837671&partnerID=8YFLogxK
U2 - 10.21660/2018.49.3534
DO - 10.21660/2018.49.3534
M3 - Article
AN - SCOPUS:85048837671
SN - 2186-2982
VL - 15
SP - 59
EP - 64
JO - International Journal of GEOMATE
JF - International Journal of GEOMATE
IS - 49
ER -