TY - GEN
T1 - Virtual screening based on pharmacophore to discover host ER alpha- glucosidase II inhibitor for dengue therapy
AU - Ariavianti, Elsafira
AU - Stephanie, Filia
AU - Tambunan, Usman Sumo Friend
N1 - Publisher Copyright:
© 2020 Trans Tech Publications Ltd, Switzerland.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Dengue is one of the crucial diseases in human-caused by dengue virus (DENV) infection. However, the development of DENV antiviral is often facing a problem because no effective drug to treat infection caused by all DENV serotypes. The inhibition of host protein involved in DENV life cycle can be a potential approach in dengue drug discovery, and also avoiding antiviral resistance. Endoplasmic Reticulum (ER) alpha-glucosidase II is one of the target host protein in DENV endoplasmic reticulum that plays an important role in the maturation process of DENV envelope glycoprotein. In this research, pharmacophore-based virtual screening and molecular docking simulations were performed to find ligand that has potential to inhibit alpha-glucosidase II activity. About 67,609 natural products from InterBioScreen (IBS) database were used in the simulation as ligands with alpha-glucosidase II as the protein target. After subjected to Lipinski’s Rule of Five, drug-likeness, nasty functions, and toxicity screening using DataWarrior software, 17,462 ligands were obtained. The pharmacophore features for molecular docking simulation was obtained from Protein-Ligand Interaction Fingerprint (PLIF) analysis using eight alpha-glucosidase II protein with different ligands. Based on virtual screening, rigid, and flexible docking simulations using Molecular Operating Environment (MOE) software, 32 ligands have lower Gibbs free binding energy (ΔGbinding) compared to the standards. The best ligand, namely STOCK1N-86400 which belongs to alkaloid derivative, showed the exceptional ligand interaction and had the lowest ΔGbinding of - 10.276 kcal/mol. The ligand was identified to have a binding interaction with amino acid Asp564 and Asp640 in alpha-glucosidase II catalytic site. The STOCK1N-86400 was also identified to have good pharmacological properties after subjected to ADME-tox test using Toxtree, SwissADME, admetSAR, and pkCSM software.
AB - Dengue is one of the crucial diseases in human-caused by dengue virus (DENV) infection. However, the development of DENV antiviral is often facing a problem because no effective drug to treat infection caused by all DENV serotypes. The inhibition of host protein involved in DENV life cycle can be a potential approach in dengue drug discovery, and also avoiding antiviral resistance. Endoplasmic Reticulum (ER) alpha-glucosidase II is one of the target host protein in DENV endoplasmic reticulum that plays an important role in the maturation process of DENV envelope glycoprotein. In this research, pharmacophore-based virtual screening and molecular docking simulations were performed to find ligand that has potential to inhibit alpha-glucosidase II activity. About 67,609 natural products from InterBioScreen (IBS) database were used in the simulation as ligands with alpha-glucosidase II as the protein target. After subjected to Lipinski’s Rule of Five, drug-likeness, nasty functions, and toxicity screening using DataWarrior software, 17,462 ligands were obtained. The pharmacophore features for molecular docking simulation was obtained from Protein-Ligand Interaction Fingerprint (PLIF) analysis using eight alpha-glucosidase II protein with different ligands. Based on virtual screening, rigid, and flexible docking simulations using Molecular Operating Environment (MOE) software, 32 ligands have lower Gibbs free binding energy (ΔGbinding) compared to the standards. The best ligand, namely STOCK1N-86400 which belongs to alkaloid derivative, showed the exceptional ligand interaction and had the lowest ΔGbinding of - 10.276 kcal/mol. The ligand was identified to have a binding interaction with amino acid Asp564 and Asp640 in alpha-glucosidase II catalytic site. The STOCK1N-86400 was also identified to have good pharmacological properties after subjected to ADME-tox test using Toxtree, SwissADME, admetSAR, and pkCSM software.
KW - Dengue virus
KW - Host ER alpha-glucosidase II
KW - InterBioScreen database
KW - Natural products
KW - Pharmacophore
UR - http://www.scopus.com/inward/record.url?scp=85085172857&partnerID=8YFLogxK
M3 - Conference contribution
AN - SCOPUS:85085172857
SN - 9783035716139
T3 - Key Engineering Materials
SP - 221
EP - 229
BT - Symposium of Materials Science and Chemistry II
A2 - Wahyuningsih, Tutik Dwi
A2 - Roto, Roto
A2 - Siswanta, Dwi
A2 - Adnan, Rohana
A2 - Commeiras, Laurent
A2 - Triyana, Kuwat
A2 - Triyana, Kuwat
A2 - Kartini, Indriana
A2 - Motuzas, Julius
PB - Trans Tech Publications Ltd
T2 - 5th International Conference on Science and Technology, ICST 2019
Y2 - 30 July 2019 through 31 July 2019
ER -
