In silico design of fragment-based drug targeting host processing α-glucosidase i for dengue fever

Dengue is a major health problem in the tropical and sub-tropical regions. The development of antiviral that targeting dengue's host enzyme can be more effective and efficient treatment than the viral enzyme. Host enzyme processing α-glucosidase I has an important role in the maturation process...

Full description

Saved in:
Bibliographic Details
Published in:IOP conference series. Materials Science and Engineering 2017-02, Vol.172 (1), p.12017, Article 012017
Main Authors: Toepak, E P, Tambunan, U S F
Format: Article
Language:English
Subjects:
Affinity
Binding
Binding energy
Dengue fever
Enzymes
Fragments
Free energy
Glucosidase
Glycoproteins
Ligands
Molecular docking
Pharmacology
Tropical environments
Viral diseases
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Dengue is a major health problem in the tropical and sub-tropical regions. The development of antiviral that targeting dengue's host enzyme can be more effective and efficient treatment than the viral enzyme. Host enzyme processing α-glucosidase I has an important role in the maturation process of dengue virus envelope glycoprotein. The inhibition of processing α-glucosidase I can become a promising target for dengue fever treatment. The antiviral approach using in silico fragment-based drug design can generate drug candidates with high binding affinity. In this research, 198.621 compounds were obtained from ZINC15 Biogenic Database. These compounds were screened to find the favorable fragments according to Rules of Three and pharmacological properties. The screening fragments were docked into the active site of processing α-glucosidase I. The potential fragment candidates from the molecular docking simulation were linked with castanospermine (CAST) to generate ligands with a better binding affinity. The Analysis of ligand - enzyme interaction showed ligands with code LRS 22, 28, and 47 have the better binding free energy than the standard ligand. Ligand LRS 28 (N-2-4-methyl-5-((1S,3S,6S,7R,8R,8aR)-1,6,7,8-tetrahydroxyoctahydroindolizin-3-yl) pentyl) indolin-1-yl) propionamide) itself among the other ligands has the lowest binding free energy. Pharmacological properties prediction also showed the ligands LRS 22, 28, and 47 can be promising as the dengue fever drug candidates.
ISSN:1757-8981
1757-899X
1757-899X
DOI:10.1088/1757-899X/172/1/012017