In silico identification of potent inhibitors of heat shock protein 90 (Hsp90) from Indonesian natural product compounds as a novel approach to treat ebola virus disease

13th Joint Conference on Chemistry

Haikal, Muhammad Chandra^1 ; Fardiansyah Nasution, Mochammad Arfin^1 ; Saputro, Linggih^1 ; Tambunan, Usman Sumo Friend^1

Bioinformatics Research Group, Departement of Chemistry, Faculty of Mathematics and Natural Science, Universitas Indonesia, Depok

16424, Indonesia^1

关键词: ADME-Tox;    Ebola virus;    Heat shock protein;    Molecular docking simulations;    Natural products;   

Others  :  https://iopscience.iop.org/article/10.1088/1757-899X/509/1/012082/pdf
DOI  :  10.1088/1757-899X/509/1/012082

来源: IOP

【 摘 要 】

Heat shock protein 90 (Hsp90) is a 90-kDa molecular chaperone that has various biological functions, varying from cell cycle progression to the protein folding, that is crucial for the cancer cell development. Furthermore, the activity of Hsp90 is also essential for the replication of negative-stranded viruses as the host factor, including Ebola virus (EBOV), a virus from Filoviridae family which is responsible for causing Ebola virus disease (EVD) outbreak in Africa in 2014. Thus, the inhibition of Hsp90 can be considered as the novel approach to combat EVD. In this research, we deployed an Indonesian natural products database to perform in silico ADME-Tox screening test and a series of molecular docking simulations against the Hsp90. A total of 3,429 ligands that have been docked, about thirteen ligands have outstanding pharmacological properties, and higher binding affinity in the binding site of Hsp90 than four referred standard ligands. In the end, we conclude that 1-O-galloyl-6-O-luteoyl-a-D-glucose, euphorbianin and scutellarein 7-neohesperidoside as the best Indonesian natural product compound to inhibit Hsp90, suggesting a potential candidate to treat EVD effectively.