Antiviral Sesquiterpene Lactones from Laurus nobilis L.: Inhibition of Hepatitis C Virus and Dengue Virus Replication.
5 affiliations
- 1Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
- 2Department of Agro-Environmental Sciences, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka 819-0395, Japan.
- 3Molecular Virology, Hellenic Pasteur Institute, 11521 Athens, Greece.
- 4Division of Pharmaceutical Chemistry, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis-Zografou, 15771 Athens, Greece.
- 5Institute of Asian and Oceanic Studies, Kyushu University, Fukuoka 819-0395, Japan.
Abstract
Natural products remain indispensable scaffolds in antiviral drug discovery, particularly against high-burden viral pathogens. In this study, two major sesquiterpene lactones, dehydrocostus lactone (1) and costunolide (2), were isolated from Laurus nobilis L. leaves and evaluated for their antiviral potential against hepatitis C virus (HCV) and dengue virus (DENV). The structures of both compounds were confirmed by HRMS and 1D NMR spectroscopic analyses. In subgenomic replicon assays, the molecules inhibited HCV replication in the low-micromolar range (EC50=2.34 μM for 1 and 2.06 μM for 2) with favorable selectivity indices. In full-length HCV reporter systems, costunolide (2) displayed enhanced anti-HCV potency, reduced viral RNA and NS5A protein levels, and enhanced the suppressive effect of the clinically approved NS5A inhibitor, daclatasvir. Furthermore, costunolide (2) exhibited cross-flaviviridae activity, suppressing DENV replication (EC50=5.89 μM in replicon cells; EC50=1.27 μM post-infection in infectious virus assays), and demonstrated cooperative suppression of viral propagation along with reduced glutathione. Mechanistically, these results highlight the critical role of the sesquiterpene lactone core, and the observed enhanced combined activity between costunolide and reduced glutathione is consistent with a possible contribution of the NRF2/glutathione antioxidant axis to its anti-DENV action. Overall, this study highlights L. nobilis as a previously underexplored source of antiviral sesquiterpene lactones and establishes costunolide (2) as a promising lead against HCV and DENV, warranting further investigation across additional Flaviviridae members.
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BibTeX
@article{amen2026antiviral,
title = {{Antiviral Sesquiterpene Lactones from Laurus nobilis L.: Inhibition of Hepatitis C Virus and Dengue Virus Replication.}},
author = {Yhiya Amen and Marwa Elsbaey and George Mpekoulis and Evangelia Christou and Helena Tsimpili and Niki Vassilaki and Kuniyoshi Shimizu and Grigoris Zoidis},
journal = {Viruses},
year = {2026},
month = sep,
doi = {10.3390/v18101056},
url = {https://europepmc.org/article/MED/42943976},
note = {CC BY},
}
RIS
TY - JOUR
TI - Antiviral Sesquiterpene Lactones from Laurus nobilis L.: Inhibition of Hepatitis C Virus and Dengue Virus Replication.
AU - Yhiya Amen
AU - Marwa Elsbaey
AU - George Mpekoulis
AU - Evangelia Christou
AU - Helena Tsimpili
AU - Niki Vassilaki
AU - Kuniyoshi Shimizu
AU - Grigoris Zoidis
PY - 2026
DA - 2026/09/23
JO - Viruses
DO - 10.3390/v18101056
UR - https://europepmc.org/article/MED/42943976
AB - Natural products remain indispensable scaffolds in antiviral drug discovery, particularly against high-burden viral pathogens. In this study, two major sesquiterpene lactones, dehydrocostus lactone (1) and costunolide (2), were isolated from Laurus nobilis L. leaves and evaluated for their antiviral potential against hepatitis C virus (HCV) and dengue virus (DENV). The structures of both compounds were confirmed by HRMS and 1D NMR spectroscopic analyses. In subgenomic replicon assays, the molecules inhibited HCV replication in the low-micromolar range (EC50=2.34 μM for 1 and 2.06 μM for 2) with favorable selectivity indices. In full-length HCV reporter systems, costunolide (2) displayed enhanced anti-HCV potency, reduced viral RNA and NS5A protein levels, and enhanced the suppressive effect of the clinically approved NS5A inhibitor, daclatasvir. Furthermore, costunolide (2) exhibited cross-flaviviridae activity, suppressing DENV replication (EC50=5.89 μM in replicon cells; EC50=1.27 μM post-infection in infectious virus assays), and demonstrated cooperative suppression of viral propagation along with reduced glutathione. Mechanistically, these results highlight the critical role of the sesquiterpene lactone core, and the observed enhanced combined activity between costunolide and reduced glutathione is consistent with a possible contribution of the NRF2/glutathione antioxidant axis to its anti-DENV action. Overall, this study highlights L. nobilis as a previously underexplored source of antiviral sesquiterpene lactones and establishes costunolide (2) as a promising lead against HCV and DENV, warranting further investigation across additional Flaviviridae members.
SN - 1999-4915
ER -