TY - JOUR T1 - Environmentally-Friendly Workflow Based on Supercritical Fluid Chromatography and Tandem Mass Spectrometry Molecular Networking For the Discovery of Potent Anti-Viral Leads From Plants JF - bioRxiv DO - 10.1101/106153 SP - 106153 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 Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/02/05/106153.abstract N2 - 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. ER -