RESEARCH ARTICLE
Depsides: Lichen Metabolites Active against
Hepatitis C Virus
Thi Huyen Vu1,2, Anne-Cécile Le Lamer1,2,3, Claudia Lalli1,2, Joël Boustie1,2
,
Michel Samson2,4,5, Françoise Lohézic-Le Dévéhat1,2☯*, Jacques Le Seyec2,4,5☯*
1 CNRS, UMR-6226, Institut des Sciences Chimiques de Rennes (ISCR), Rennes, France, 2 Université de
Rennes 1, Rennes, France, 3 Université de Toulouse III, Toulouse, France, 4 INSERM, UMR-1085, Institut
de Recherche Santé Environnement & Travail (IRSET), Rennes, France, 5 Fédération de Recherche BioSit
de Rennes, Rennes, France
☯ These authors contributed equally to this work.
Abstract
A thorough phytochemical study of Stereocaulon evolutum was conducted, for the isolation
of structurally related atranorin derivatives. Indeed, pilot experiments suggested that atra-
norin (1), the main metabolite of this lichen, would interfere with the lifecycle of hepatitis
C virus (HCV). Eight compounds, including one reported for the first time (2), were isolated
and characterized. Two analogs (5, 6) were also synthesized, to enlarge the panel of atra-
norin-related structures. Most of these compounds were active against HCV, with a half-
maximal inhibitory concentration of about 10 to 70 µM, with depsides more potent than
monoaromatic phenols. The most effective inhibitors (1, 5 and 6) were then added at differ-
ent steps of the HCV lifecycle. Interestingly, atranorin (1), bearing an aldehyde function at
C-3, inhibited only viral entry, whereas the synthetic compounds 5 and 6, bearing a hydroxy-
methyl and a methyl function, respectively, at C-3 interfered with viral replication.
OPEN ACCESS
Citation: Vu TH, Le Lamer A-C, Lalli C, Boustie J,
Samson M, Lohézic-Le Dévéhat F, et al. (2015)
Depsides: Lichen Metabolites Active against Hepatitis
C Virus. PLoS ONE 10(3): e0120405. doi:10.1371/
journal.pone.0120405
Academic Editor: Gabriele Berg, Graz University of
Technology (TU Graz), AUSTRIA
Received: July 21, 2014
Accepted: January 25, 2015
Published: March 20, 2015
Copyright: © 2015 Vu et al. This is an open access
article distributed under the terms of the Creative
unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are
credited.
Introduction
Hepatitis C virus (HCV) is a small, enveloped virus of genus Hepacivirus, from the Flaviviridae
family. About 170 million people worldwide are chronically infected with HCV, and there are
three to four million new infections each year [1], principally through blood transmission. The
high genetic variability of the virus has hindered vaccine development. However, new treat-
ments have emerged in the last few years, with the discovery of direct-acting antivirals (DAAs),
which were added to the previous standard care procedure based on the use of pegylated inter-
feron (IFN) and ribavirin (RVB). Clinical trials currently underway suggest that IFN-free regi-
mens combining several DAAs will cure almost all cases of hepatitis C, making it possible to
avoid the severe adverse effects of IFN treatment [2]. Nevertheless, the current high cost of
such treatments may restrict them to only the wealthiest patients and nations [3]. There is,
therefore, still a need to develop alternative and complementary approaches to treatment for a
large proportion of patients.
Data Availability Statement: All relevant data are
within the paper and its Supporting Information files.
Funding: This research was supported by the
Biology and Health Federative Research Structure of
Rennes (Biosit, UMS CNRS 3480 / US INSERM
018), by the Comité Grand-Ouest de la Ligue contre
le Cancer, by the "Institute National de la Santé Et de
la Recherche Médicale" (INSERM), by the "Université
de Rennes 1" and by the "Centre National de
Recherche Scientifique" (CNRS). THV. is supported
by a scholarship from the Vietnamese Government
(Project 322, Ministry of Education and Training). The
funder had no role in study design, data collection
PLOS ONE | DOI:10.1371/journal.pone.0120405 March 20, 2015
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