Muchtaridi, Muchtaridi
(2013)
Computer-Aided Drug Design Of
Potential Neuraminidase Inhibitors
From Plant Extracts.
PhD thesis, Universiti Sains Malaysia.
Abstract
Neuraminidase (NA) of influenza virus is responsible for the proliferation and
infections of the virus progeny, prompting several efforts to discover and optimize
new neuraminidase inhibitors. The main aim of this study is to discover new
potential neuraminidase inhibitor from the natural product source using computeraided
(pharmacophore modelling-molecular docking) drug design method combined
with bioassay-guided isolation. Two Hypogen models were selected as screening
sievers (ROC AUC =0.91 and 0.80; ݎ
ଶ = 0.92 and 0.90). These models were
integrated with molecular docking to screen 3000 compounds from NADI database.
Virtual screening results showed that xanthone derivatives from G. mangostana
(mangosteen) were the top hits, thus provide rationale to select this plant for further
isolation. Seven compounds obtained from mangosteen showed inhibition more than
80 % by bioassay-guided isolation. The potency of neuraminidase (NA) (C.
perfringens-NA and H1N1-NA) inhibitory effect in this study is as follows:
garcinone D > -mangostin > -mangostin > garcinone C > 3-isomangostin >
gartanin > 8-deoxygartanin. These seven compounds were favourably docked to the
binding site of NA.
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