PT - JOURNAL ARTICLE AU - Louis-Félix Nothias AU - Stéphanie Boutet-Mercey AU - Xavier Cachet AU - Erick De La Torre AU - Laurent Laboureur AU - Jean-François Gallard AU - Pascal Retailleau AU - Alain Brunelle AU - Pieter C. Dorrestein AU - Jean Costa AU - Luis M. Bedoya AU - Fanny Roussi AU - Pieter Leyssen AU - José Alcami AU - Julien Paolini AU - Marc Litaudon AU - David Touboul TI - Environmentally-Friendly Workflow Based on Supercritical Fluid Chromatography and Tandem Mass Spectrometry Molecular Networking For the Discovery of Potent Anti-Viral Leads From Plants AID - 10.1101/106153 DP - 2017 Jan 01 TA - bioRxiv PG - 106153 4099 - http://biorxiv.org/content/early/2017/02/05/106153.short 4100 - http://biorxiv.org/content/early/2017/02/05/106153.full AB - A supercritical fluid chromatography-based targeted purification workflow using tandem mass spectrometry and molecular networking was developed to analyze, annotate and isolate secondary metabolites from complex mixture. This approach was applied for targeted isolation of new antiviral diterpene esters from Euphorbia semiperfoliata whole plant extract. The analysis of bioactive fractions revealed that unknown diterpene esters, including jatrophane esters and phorboids esters, were present in the samples. The purification procedure using semi-preparative-supercritical fluid chromatography led to the isolation and identification of two jatrophane esters (13 and 14) and four 4-deoxyphorbol esters (15-18). Compound 16 was found to display antiviral activity against chikungunya virus (EC50 = 0.45 µM), while compound 15 was found to be a potent and selective inhibitor of HIV-1 replication in a recombinant virus assay (EC50 = 13 nM). This study showed that supercritical fluid chromatography-based workflow and molecular networking can facilitate and accelerate the discovery of bioactive small molecules by targeted molecules of interest, while minimizing the use of toxic solvents.