TY - JOUR
T1 - 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
AU - Haikal, Muhammad Chandra
AU - Fardiansyah Nasution, Mochammad Arfin
AU - Saputro, Linggih
AU - Friend Tambunan, Usman Sumo
N1 - Funding Information:
The Author would like to thank Directorate of Research and Community Engagements, Universitas Indonesia, and Ministry of Research, Technology, and Higher Education, Republic of Indonesia for funding this research through Hibah Penelitian Kerjasama Luar Negeri (PKLN) 2018 No: 538/UN2.R3.1/HKP.05.00/2018.
Publisher Copyright:
© 2019 Published under licence by IOP Publishing Ltd.
PY - 2019/5/3
Y1 - 2019/5/3
N2 - 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.
AB - 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.
KW - Ebola virus (EBOV)
KW - Heat shock protein (Hsp90)
KW - in silico ADME-Tox screening test
KW - Indonesian natural product
KW - Molecular docking simulation
UR - http://www.scopus.com/inward/record.url?scp=85065613006&partnerID=8YFLogxK
U2 - 10.1088/1757-899X/509/1/012082
DO - 10.1088/1757-899X/509/1/012082
M3 - Conference article
AN - SCOPUS:85065613006
VL - 509
JO - IOP Conference Series: Materials Science and Engineering
JF - IOP Conference Series: Materials Science and Engineering
SN - 1757-8981
IS - 1
M1 - 012082
T2 - 13th Joint Conference on Chemistry, JCC 2018
Y2 - 7 September 2018 through 8 September 2018
ER -