title: Chemical diversity and antiviral potential in the pantropical Diospyros genus.
abstract: A screening using a dengue replicon virus-cell-based assay was performed on 3563 ethyl acetate (EtOAc) extracts from different parts of 1500 plants. The screening led to the selection of species from the genus Diospyros (Ebenaceae), among which 25 species distributed in tropical areas showed significant inhibitory activity on dengue virus replication. A metabolic analysis was conducted from the UPLC-HRMS profiles of 33 biologically active and inactive plant extracts, and their metabolic proximity is presented in the form of a dendrogram. The results of the study showed that chemical similarity is not related to plant species or organ. Overall, metabolomic profiling allowed us to define large groups of extracts, comprising both active and inactive ones. Closely related profiles from active extracts might indicate that the common major components of these extracts were responsible for the antiviral activity, while the comparison of chemically similar active and inactive extracts, will permit to find compounds of interest. Eventually, the phytochemical investigation of Diospyros glans bark EtOAc extract afforded usnic acid and 7 known ursane- and lupane-type triterpenoids, among which 5 were found significantly active against dengue virus replication. The inhibitory potency of these compounds was also evaluated on a DENV-NS5 RNA-dependant RNA polymerase assay.
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS, UPR2301, University Paris-Saclay, 91198-Gif-sur-Yvette, Cedex, France.
authors.forename: Laure-Anne
authors.initials: LA
authors.lastname: Peyrat
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS, UPR2301, University Paris-Saclay, 91198-Gif-sur-Yvette, Cedex, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Eparvier
authors.affiliation: Centre de Recherche Architecture et Fonction des Macromolécules Biologiques, UMR 7257 CNRS, Aix-Marseille University, 163 Avenue de Luminy, 13288 Marseille Cedex, France.
authors.forename: Cécilia
authors.initials: C
authors.lastname: Eydoux
authors.affiliation: Centre de Recherche Architecture et Fonction des Macromolécules Biologiques, UMR 7257 CNRS, Aix-Marseille University, 163 Avenue de Luminy, 13288 Marseille Cedex, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Guillemot
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS, UPR2301, University Paris-Saclay, 91198-Gif-sur-Yvette, Cedex, France; Sorbonne Universités, UPMC Univ Paris 06, CNRS, Laboratoire de Biodiversité et Biotechnologies Microbiennes (LBBM), Observatoire Océanologique, 66650-Banyuls-sur-mer, France. Electronic address: didier.stien@cnrs.fr.
authors.forename: Didier
authors.initials: D
authors.lastname: Stien
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS, UPR2301, University Paris-Saclay, 91198-Gif-sur-Yvette, Cedex, France. Electronic address: marc.litaudon@cnrs.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Litaudon
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000302:isolation & purification; D001572:Benzofurans / Q000737:chemistry / Q000302:isolation & purification; D019556:COS Cells; D002522:Chlorocebus aethiops; D003716:Dengue Virus / Q000187:drug effects* / Q000502:physiology; D029788:Diospyros / Q000737:chemistry*; D055442:Metabolome; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D001572:Benzofurans; D010936:Plant Extracts; D014315:Triterpenes; C073339:usnic acid
keywords: Dengue virus; Diospyros glans; Diospyros spp.; Ebenaceae; MZmine; Triterpenoids