Identification of natural products as an inhibitor of β-OG pocket binder of dengue virus envelope protein using fragment-based drug design and molecular docking approach

Usman Sumo Friend, A. H. Alkaff

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

2 Citations (Scopus)

Abstract

Dengue fever remains as a serious infectious disease that can have horrible consequences, including death. Although it is not a new disease, there is no effective antiviral drug available to treat this disease. In this study, fragment-based drug design and molecular docking approach have been done to generate the potential drug candidates for inhibiting β-OG pocket binder of the envelope protein responsible for mediating DENV entry into the host cell. About 190,084 natural product compounds were obtained from ZINC15 database. The rules of three and pharmacological test were employed against the natural product compounds, resulting 1,610 favorable fragments. These fragments were docked into the polar and nonpolar regions of β-OG pocket binder cavity, respectively. The potential fragments, which bound to each region, were linked to generate 6,487 ligands. The rules of five and pharmacological test against the ligands have been done to discard the ligands with the undesired molecular properties. The inhibition activity of 2,950 ligands was evaluated by employing rigid and flexible molecular docking simulation. AX1312, AZ0830, and AZ0492 show a promising potential as the drug leading candidate for treating dengue fever as they have a better binding free energy and molecular interaction with DENV envelope protein compared to the standard compound, n-octyl-β-D-glucoside. Further in vitro and in vivo analysis are required to validate their inhibition activity against DENV envelope protein under actual biological condition.

Original languageEnglish
Title of host publicationProceedings of the 3rd International Symposium on Current Progress in Mathematics and Sciences 2017, ISCPMS 2017
EditorsRatna Yuniati, Terry Mart, Ivandini T. Anggraningrum, Djoko Triyono, Kiki A. Sugeng
PublisherAmerican Institute of Physics Inc.
ISBN (Electronic)9780735417410
DOIs
Publication statusPublished - 22 Oct 2018
Event3rd International Symposium on Current Progress in Mathematics and Sciences 2017, ISCPMS 2017 - Bali, Indonesia
Duration: 26 Jul 201727 Jul 2017

Publication series

NameAIP Conference Proceedings
Volume2023
ISSN (Print)0094-243X
ISSN (Electronic)1551-7616

Conference

Conference3rd International Symposium on Current Progress in Mathematics and Sciences 2017, ISCPMS 2017
Country/TerritoryIndonesia
CityBali
Period26/07/1727/07/17

Keywords

  • Dengue virus
  • dengue virus envelope
  • fragment-based drug design
  • molecular docking simulation
  • natural product compounds

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