Natural products (NP) are a valuable drug resource. However, NP-inspired drug leads are declining, among other reasons due to high re-discovery rates. We developed a conceptual framework using the metabolic fingerprint of entire ecosystems (MeE) to facilitate the discovery of global bioactivity hotspots. We assessed the MeE of 305 sites of diverse aquatic ecosystems, worldwide. All samples were tested for antiviral effects against the human immunodeficiency virus (HIV), followed by a comprehensive screening for cell-modulatory activity by High-Content Screening (HCS). We discovered a very strong HIV-1 inhibition mainly in samples taken from fjords with a strong terrestrial input. Multivariate data integration demonstrated an association of a set of polyphenols with specific biological alterations (endoplasmic reticulum, lysosomes, and NFkB) caused by these samples. Moreover, we found strong HIV-1 inhibition in one unrelated oceanic sample closely matching to HIV-1-inhibitory drugs on a cytological and a chemical level. Taken together, we demonstrate that even without physical purification, a sophisticated strategy of differential filtering, correlation analysis, and multivariate statistics can be employed to guide chemical analysis, to improve de-replication, and to identify ecosystems with promising characteristics as sources for NP discovery.
Conflict of interest statement
The authors declare no competing interests.
Translational Metabolomics of Head Injury: Exploring Dysfunctional Cerebral Metabolism with Ex Vivo NMR Spectroscopy-Based Metabolite Quantification.In: Kobeissy FH, editor. Brain Neurotrauma: Molecular, Neuropsychological, and Rehabilitation Aspects. Boca Raton (FL): CRC Press/Taylor & Francis; 2015. Chapter 25. Brain Neurotrauma: Molecular, Neuropsychological, and Rehabilitation Aspects. 2015. PMID: 26269925 Free Books & Documents. Review.
Exploring conceptual and theoretical frameworks for nurse practitioner education: a scoping review protocol.JBI Database System Rev Implement Rep. 2015 Oct;13(10):146-55. doi: 10.11124/jbisrir-2015-2150. JBI Database System Rev Implement Rep. 2015. PMID: 26571290 Review.
[Aiming for zero blindness].Nippon Ganka Gakkai Zasshi. 2015 Mar;119(3):168-93; discussion 194. Nippon Ganka Gakkai Zasshi. 2015. PMID: 25854109 Review. Japanese.
[Development of antituberculous drugs: current status and future prospects].Kekkaku. 2006 Dec;81(12):753-74. Kekkaku. 2006. PMID: 17240921 Review. Japanese.
Review on environmental alterations propagating from aquatic to terrestrial ecosystems.Sci Total Environ. 2015 Dec 15;538:246-61. doi: 10.1016/j.scitotenv.2015.08.038. Epub 2015 Aug 24. Sci Total Environ. 2015. PMID: 26311581 Review.