Bioprospecting of Red Sea Sponges for Novel Antiviral Pharmacophores

Handle URI:
http://hdl.handle.net/10754/552842
Title:
Bioprospecting of Red Sea Sponges for Novel Antiviral Pharmacophores
Authors:
O'Rourke, Aubrie ( 0000-0003-1277-9536 )
Abstract:
Natural products offer many possibilities for the treatment of disease. More than 70% of the Earth’s surface is ocean, and recent exploration and access has allowed for new additions to this catalog of natural treasures. The Central Red Sea off the coast of Saudi Arabia serves as a newly accessible location, which provides the opportunity to bioprospect marine sponges with the purpose of identifying novel antiviral scaffolds. Antivirals are underrepresented in present day clinical trials, as well as in the academic screens of marine natural product libraries. Here a high-throughput pipeline was initiated by prefacing the antiviral screen with an Image-based High-Content Screening (HCS) technique in order to identify candidates with antiviral potential. Prospective candidates were tested in a biochemical or cell-based assay for the ability to inhibit the NS3 protease of the West Nile Virus (WNV NS protease) as well as replication and reverse transcription of the Human Immunodeficiency Virus 1 (HIV-1). The analytical chemistry techniques of High-Performance Liquid Chromatograpy (HPLC), Liquid Chromatography-Mass Spectrometry (LC-MS), and Nuclear Magnetic Resonance (NMR) where used in order to identify the compounds responsible for the characteristic antiviral activity of the selected sponge fractions. We have identified a 3-alkyl pyridinium from Amphimedon chloros as the causative agent of the observed WNV NS3 protease inhibition in vitro. Additionally, we identified debromohymenialdisine, hymenialdisine, and oroidin from Stylissa carteri as prospective scaffolds capable of HIV-1 inhibition.
Advisors:
Voolstra, Christian R. ( 0000-0003-4555-3795 )
Committee Member:
Stingl, Ulrich ( 0000-0002-0684-2597 ) ; Khashab, Niveen M. ( 0000-0003-2728-0666 ) ; Brack-Werner, Ruth
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
Program:
Marine Science
Issue Date:
May-2015
Type:
Dissertation
Appears in Collections:
Marine Science Program; Dissertations; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.advisorVoolstra, Christian R.en
dc.contributor.authorO'Rourke, Aubrieen
dc.date.accessioned2015-05-14T11:52:34Zen
dc.date.available2015-05-14T11:52:34Zen
dc.date.issued2015-05en
dc.identifier.urihttp://hdl.handle.net/10754/552842en
dc.description.abstractNatural products offer many possibilities for the treatment of disease. More than 70% of the Earth’s surface is ocean, and recent exploration and access has allowed for new additions to this catalog of natural treasures. The Central Red Sea off the coast of Saudi Arabia serves as a newly accessible location, which provides the opportunity to bioprospect marine sponges with the purpose of identifying novel antiviral scaffolds. Antivirals are underrepresented in present day clinical trials, as well as in the academic screens of marine natural product libraries. Here a high-throughput pipeline was initiated by prefacing the antiviral screen with an Image-based High-Content Screening (HCS) technique in order to identify candidates with antiviral potential. Prospective candidates were tested in a biochemical or cell-based assay for the ability to inhibit the NS3 protease of the West Nile Virus (WNV NS protease) as well as replication and reverse transcription of the Human Immunodeficiency Virus 1 (HIV-1). The analytical chemistry techniques of High-Performance Liquid Chromatograpy (HPLC), Liquid Chromatography-Mass Spectrometry (LC-MS), and Nuclear Magnetic Resonance (NMR) where used in order to identify the compounds responsible for the characteristic antiviral activity of the selected sponge fractions. We have identified a 3-alkyl pyridinium from Amphimedon chloros as the causative agent of the observed WNV NS3 protease inhibition in vitro. Additionally, we identified debromohymenialdisine, hymenialdisine, and oroidin from Stylissa carteri as prospective scaffolds capable of HIV-1 inhibition.en
dc.language.isoenen
dc.subjectAntiviralsen
dc.subjectRed Seaen
dc.subjectSpongesen
dc.subjectWest Nile Virusen
dc.subjectHIV-Ien
dc.subjectNatural productsen
dc.titleBioprospecting of Red Sea Sponges for Novel Antiviral Pharmacophoresen
dc.typeDissertationen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
thesis.degree.grantorKing Abdullah University of Science and Technologyen_GB
dc.contributor.committeememberStingl, Ulrichen
dc.contributor.committeememberKhashab, Niveen M.en
dc.contributor.committeememberBrack-Werner, Ruthen
thesis.degree.disciplineMarine Scienceen
thesis.degree.nameDoctor of Philosophyen
dc.person.id122109en
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