title: Alkaloids from the Sponge Stylissa carteri Present Prospective Scaffolds for the Inhibition of Human Immunodeficiency Virus 1 (HIV-1).
abstract: The sponge Stylissa carteri is known to produce a number of secondary metabolites displaying anti-fouling, anti-inflammatory, and anti-cancer activity. However, the anti-viral potential of metabolites produced by S. carteri has not been extensively explored. In this study, an S. carteri extract was HPLC fractionated and a cell based assay was used to evaluate the effects of HPLC fractions on parameters of Human Immunodeficiency Virus (HIV-1) infection and cell viability. Candidate HIV-1 inhibitory fractions were then analyzed for the presence of potential HIV-1 inhibitory compounds by mass spectrometry, leading to the identification of three previously characterized compounds, i.e., debromohymenialdisine (DBH), hymenialdisine (HD), and oroidin. Commercially available purified versions of these molecules were re-tested to assess their antiviral potential in greater detail. Specifically, DBH and HD exhibit a 30%-40% inhibition of HIV-1 at 3.1 μM and 13 μM, respectively; however, both exhibited cytotoxicity. Conversely, oroidin displayed a 50% inhibition of viral replication at 50 μM with no associated toxicity. Additional experimentation using a biochemical assay revealed that oroidin inhibited the activity of the HIV-1 Reverse Transcriptase up to 90% at 25 μM. Taken together, the chemical search space was narrowed and previously isolated compounds with an unexplored anti-viral potential were found. Our results support exploration of marine natural products for anti-viral drug discovery.
authors: Red Sea Research Center, Division of Biological and Environmental Science and Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia. aubrie.orourke@kaust.edu.sa.
authors: Aubrie
authors: A
authors: O'Rourke
authors: Red Sea Research Center, Division of Biological and Environmental Science and Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia. stephangeorg.kremb@kaust.edu.sa.
authors: Stephan
authors: S
authors: Kremb
authors: Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum Muenchen, 85764 Neuherberg, Germany. theresa.bader@helmholtz-muenchen.de.
authors: Theresa Maria
authors: TM
authors: Bader
authors: Institute of Virology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany. brack@helmholtz-muenchen.de.
authors: Markus
authors: M
authors: Helfer
authors: Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum Muenchen, 85764 Neuherberg, Germany. schmitt-kopplin@helmholtz-muenchen.de.|Analytical Food Chemistry, Technical University of Munich, 85354 Freising Weihenstephan, Germany. schmitt-kopplin@helmholtz-muenchen.de.
authors: Philippe
authors: P
authors: Schmitt-Kopplin
authors: Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. wgerwick@ucsd.edu.
authors: William H
authors: WH
authors: Gerwick
authors: Institute of Virology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany. brack@helmholtz-muenchen.de.
authors: Ruth
authors: R
authors: Brack-Werner
authors: Red Sea Research Center, Division of Biological and Environmental Science and Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia. christian.voolstra@kaust.edu.sa.
authors: Christian R
authors: CR
authors: Voolstra
mesh_terms: D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D019380:Anti-HIV Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D011161:Porifera / Q000378:metabolism*; D064210:Secondary Metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000470:Alkaloids; D019380:Anti-HIV Agents; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase
keywords: HIV-1; Red Sea; Stylissa carteri; marine bioprospecting; reverse transcriptase