Potential Neuraminidase Inhibitors Via Virtual Screening, Kinetic Studies, And Adme Predictions

Aktiviti neuraminidase (NA) memainkan peranan yang penting dalam jangkitan oleh virus influenza dengan memudahkan pelepasan virion yang baru ditubuhkan daripada reseptor sel tuan rumah dan menggalakkan jangkitan kepada selsel atau organ-organ lain. Disebabkan kemunculan rintangan virus terhadap p...

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Main Author:	Nuwarda, Rina Fajri
Format:	Thesis
Language:	English
Published:	2015
Subjects:	RS1-441 Pharmacy and materia medica
Online Access:	http://eprints.usm.my/31990/1/RINA_FAJRI_NUWARDA_24%28NN%29.pdf
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spelling	my-usm-ep.319902019-04-12T05:25:36Z Potential Neuraminidase Inhibitors Via Virtual Screening, Kinetic Studies, And Adme Predictions 2015-10 Nuwarda, Rina Fajri RS1-441 Pharmacy and materia medica Aktiviti neuraminidase (NA) memainkan peranan yang penting dalam jangkitan oleh virus influenza dengan memudahkan pelepasan virion yang baru ditubuhkan daripada reseptor sel tuan rumah dan menggalakkan jangkitan kepada selsel atau organ-organ lain. Disebabkan kemunculan rintangan virus terhadap perencat NA sedia ada, penemuan perencat NA baru amat diperlukan. Dalam kajian ini, pemeriksaan maya berdasarkan pendokan sebatian-sebatian daripada pangkalan data NCI untuk memilih dengan pantas hit in silico bagi menjadi potensi perencat NA telah dijalankan. Satu kaedah in vitro baru telah dicuba untuk membangunkan perencatan asai NA dengan menggunakan teknologi AlphaScreenTM dengan Alpha-1-Asid Glikoprotein sebagai substrat. Malangnya, usaha ini tidak berjaya mungkin disebabkan pemisahan tidak spesifik asid sialik oleh NA. Selepas itu, asai MUNANA tradisional telah dijalankan untuk menyiasat aktiviti perencatan dan parameter kinetik sebatian perencat. Akhir sekali, sebatian-sebatian terpilih dikaji untuk ciri farmakokinetik in silico mereka. Dari pangkalan data NCI, 1541 sebatian telah berjaya disaring untuk mendapatkan 40 kompaun hit in silico diikuti oleh asai MUNANA untuk menentukan IC50 mereka. Neuraminidase (NA) activity plays an important role in the infection by influenza viruses by facilitating the release of the newly formed virions from the host cell receptor and promotes its infection to other cells or organs. With the emergence of viral resistance towards the existing NA inhibitors, the discovery of new NA inhibitors is urgently needed. In this work, docking-based virtual screening of large compounds from NCI database to rapidly select in silico hits to be potential NA inhibitors was carried out. A new in vitro method has been attempted to be developed for NA inhibition assay by utilizing AlphaScreenTM technology with Alpha-1-Acid glycoprotein as a substrate. Unfortunately, this effort was unsuccessful probably due to the non-specific cleavage of sialic acid by NA. Subsequently, a traditional MUNANA assay was performed to investigate the inhibitory activities and kinetic parameters of the inhibitor compounds. Finally, the selected compounds were studied for their pharmacokinetic properties in silico. From the NCI database, 1541 compounds have been successfully screened and 40 in silico hits compounds were obtained, and assayed to determine their IC50s. 2015-10 Thesis http://eprints.usm.my/31990/ http://eprints.usm.my/31990/1/RINA_FAJRI_NUWARDA_24%28NN%29.pdf application/pdf en public masters Universiti Sains Malaysia Pusat Pengajian Sains Farmasi (School of Pharmaceutical Sciences)
institution	Universiti Sains Malaysia
collection	USM Institutional Repository
language	English
topic	RS1-441 Pharmacy and materia medica
spellingShingle	RS1-441 Pharmacy and materia medica Nuwarda, Rina Fajri Potential Neuraminidase Inhibitors Via Virtual Screening, Kinetic Studies, And Adme Predictions
description	Aktiviti neuraminidase (NA) memainkan peranan yang penting dalam jangkitan oleh virus influenza dengan memudahkan pelepasan virion yang baru ditubuhkan daripada reseptor sel tuan rumah dan menggalakkan jangkitan kepada selsel atau organ-organ lain. Disebabkan kemunculan rintangan virus terhadap perencat NA sedia ada, penemuan perencat NA baru amat diperlukan. Dalam kajian ini, pemeriksaan maya berdasarkan pendokan sebatian-sebatian daripada pangkalan data NCI untuk memilih dengan pantas hit in silico bagi menjadi potensi perencat NA telah dijalankan. Satu kaedah in vitro baru telah dicuba untuk membangunkan perencatan asai NA dengan menggunakan teknologi AlphaScreenTM dengan Alpha-1-Asid Glikoprotein sebagai substrat. Malangnya, usaha ini tidak berjaya mungkin disebabkan pemisahan tidak spesifik asid sialik oleh NA. Selepas itu, asai MUNANA tradisional telah dijalankan untuk menyiasat aktiviti perencatan dan parameter kinetik sebatian perencat. Akhir sekali, sebatian-sebatian terpilih dikaji untuk ciri farmakokinetik in silico mereka. Dari pangkalan data NCI, 1541 sebatian telah berjaya disaring untuk mendapatkan 40 kompaun hit in silico diikuti oleh asai MUNANA untuk menentukan IC50 mereka. Neuraminidase (NA) activity plays an important role in the infection by influenza viruses by facilitating the release of the newly formed virions from the host cell receptor and promotes its infection to other cells or organs. With the emergence of viral resistance towards the existing NA inhibitors, the discovery of new NA inhibitors is urgently needed. In this work, docking-based virtual screening of large compounds from NCI database to rapidly select in silico hits to be potential NA inhibitors was carried out. A new in vitro method has been attempted to be developed for NA inhibition assay by utilizing AlphaScreenTM technology with Alpha-1-Acid glycoprotein as a substrate. Unfortunately, this effort was unsuccessful probably due to the non-specific cleavage of sialic acid by NA. Subsequently, a traditional MUNANA assay was performed to investigate the inhibitory activities and kinetic parameters of the inhibitor compounds. Finally, the selected compounds were studied for their pharmacokinetic properties in silico. From the NCI database, 1541 compounds have been successfully screened and 40 in silico hits compounds were obtained, and assayed to determine their IC50s.
format	Thesis
qualification_level	Master's degree
author	Nuwarda, Rina Fajri
author_facet	Nuwarda, Rina Fajri
author_sort	Nuwarda, Rina Fajri
title	Potential Neuraminidase Inhibitors Via Virtual Screening, Kinetic Studies, And Adme Predictions
title_short	Potential Neuraminidase Inhibitors Via Virtual Screening, Kinetic Studies, And Adme Predictions
title_full	Potential Neuraminidase Inhibitors Via Virtual Screening, Kinetic Studies, And Adme Predictions
title_fullStr	Potential Neuraminidase Inhibitors Via Virtual Screening, Kinetic Studies, And Adme Predictions
title_full_unstemmed	Potential Neuraminidase Inhibitors Via Virtual Screening, Kinetic Studies, And Adme Predictions
title_sort	potential neuraminidase inhibitors via virtual screening, kinetic studies, and adme predictions
granting_institution	Universiti Sains Malaysia
granting_department	Pusat Pengajian Sains Farmasi (School of Pharmaceutical Sciences)
publishDate	2015
url	http://eprints.usm.my/31990/1/RINA_FAJRI_NUWARDA_24%28NN%29.pdf
_version_	1747820514442739712

Potential Neuraminidase Inhibitors Via Virtual Screening, Kinetic Studies, And Adme Predictions

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