Computer-Aided Drug Design Of Potential Neuraminidase Inhibitors From Plant Extracts

• Main Author: Muchtaridi, Muchtaridi
• Format: Thesis
• Language: English
• Published: 2013
• Subjects: RS1-441 Pharmacy and materia medica
• Online Access: http://eprints.usm.my/43839/

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.