Identification Of Potential Neuraminidase Inhibitors Using Ensemble-Based Virtual Screening
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Date
2013-11
Authors
Lim, Kok Keong
Journal Title
Journal ISSN
Volume Title
Publisher
Universiti Sains Malaysia
Abstract
To date, influenza A virus cause a serious impact in human health. It has
emerged as a worldwide pandemic threat in the 21st century where large human
populations were affected annually. At present, Oseltamivir (Tamiflu) and Zanamivir
(Relenza) have become important treatments for influenza infectious disease.
Unfortunately, the resistance of influenza viruses to these drugs has been reported
recently. So, it is important to discover new anti-influenza inhibitors to overcome the
on-going and potential influenza outbreak. This project is about the discovery of the
potential inhibitor for influenza infectious disease via ensemble-based virtual
screening. As a receptor destroying enzyme, neuraminidase has been widely used as
a drug target for drug discovery. Thus, this study was focused on Neuraminidase
subtype-1. Variation of neuraminidase conformations from Protein Data Bank (PDB)
and molecular dynamics (MD) simulation structures were used in this study. With
the aid of computational resource, ensemble-based virtual screening was performed.
Neuraminidase was screened against the National Cancer Institute (NCI) Database
and the Natural Product Discovery System (NADI) Database to discover the
potential compounds as the neuraminidase inhibitors. From docking results, 20
compounds from NCI Database were selected. For NADI Database, there were 40
compounds have been selected and they were clustered into 7 plants. All these
compounds (NCI and NADI) were able to bind to all 13 ensemble structures. This
has exhibited the probable anti-neuraminidase activity. These compounds were then
subjected to inhibitory activity evaluation via MUNANA assay.
Description
Keywords
Neuraminidase Inhibitors , Virtual Screening