Luteolin Isolated from <i>Juncus acutus</i> L., a Potential Remedy for Human Coronavirus 229E

The COVID-19 pandemic, caused by SARS-CoV-2, addressed the lack of specific antiviral drugs against coronaviruses. In this study, bioguided fractionation performed on both ethyl acetate and aqueous sub-extracts of <i>Juncus acutus</i> stems led to identifying luteolin as a highly active...

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Main Authors: Asma Hakem, Lowiese Desmarets, Ramla Sahli, Rawen Ben Malek, Charline Camuzet, Nathan François, Gabriel Lefèvre, Jennifer Samaillie, Sophie Moureu, Sevser Sahpaz, Sandrine Belouzard, Riadh Ksouri, Karin Séron, Céline Rivière
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/28/11/4263
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author Asma Hakem
Lowiese Desmarets
Ramla Sahli
Rawen Ben Malek
Charline Camuzet
Nathan François
Gabriel Lefèvre
Jennifer Samaillie
Sophie Moureu
Sevser Sahpaz
Sandrine Belouzard
Riadh Ksouri
Karin Séron
Céline Rivière
author_facet Asma Hakem
Lowiese Desmarets
Ramla Sahli
Rawen Ben Malek
Charline Camuzet
Nathan François
Gabriel Lefèvre
Jennifer Samaillie
Sophie Moureu
Sevser Sahpaz
Sandrine Belouzard
Riadh Ksouri
Karin Séron
Céline Rivière
author_sort Asma Hakem
collection DOAJ
description The COVID-19 pandemic, caused by SARS-CoV-2, addressed the lack of specific antiviral drugs against coronaviruses. In this study, bioguided fractionation performed on both ethyl acetate and aqueous sub-extracts of <i>Juncus acutus</i> stems led to identifying luteolin as a highly active antiviral molecule against human coronavirus HCoV-229E. The apolar sub-extract (CH<sub>2</sub>Cl<sub>2</sub>) containing phenanthrene derivatives did not show antiviral activity against this coronavirus. Infection tests on Huh-7 cells, expressing or not the cellular protease TMPRSS2, using luciferase reporter virus HCoV-229E-Luc showed that luteolin exhibited a dose-dependent inhibition of infection. Respective IC<sub>50</sub> values of 1.77 µM and 1.95 µM were determined. Under its glycosylated form (luteolin-7-<i>O</i>-glucoside), luteolin was inactive against HCoV-229E. Time of addition assay showed that utmost anti-HCoV-229E activity of luteolin was achieved when added at the post-inoculation step, indicating that luteolin acts as an inhibitor of the replication step of HCoV-229E. Unfortunately, no obvious antiviral activity for luteolin was found against SARS-CoV-2 and MERS-CoV in this study. In conclusion, luteolin isolated from <i>Juncus acutus</i> is a new inhibitor of alphacoronavirus HCoV-229E.
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spelling doaj.art-b0aecfc6f0084a2fa392f6da4d09db6b2023-11-18T08:14:14ZengMDPI AGMolecules1420-30492023-05-012811426310.3390/molecules28114263Luteolin Isolated from <i>Juncus acutus</i> L., a Potential Remedy for Human Coronavirus 229EAsma Hakem0Lowiese Desmarets1Ramla Sahli2Rawen Ben Malek3Charline Camuzet4Nathan François5Gabriel Lefèvre6Jennifer Samaillie7Sophie Moureu8Sevser Sahpaz9Sandrine Belouzard10Riadh Ksouri11Karin Séron12Céline Rivière13Joint Research Unit 1158, BioEcoAgro, Univ. Lille, INRAE, Univ. Liège, UPJV, JUNIA, Univ. Artois, Univ. Littoral Côte d’Opale, ICV—Institut Charles Viollette, 59650 Villeneuve–d’Ascq, FranceCenter for Infection and Immunity of Lille (CIIL), Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019—UMR 9017, 59000 Lille, FranceJoint Research Unit 1158, BioEcoAgro, Univ. Lille, INRAE, Univ. Liège, UPJV, JUNIA, Univ. Artois, Univ. Littoral Côte d’Opale, ICV—Institut Charles Viollette, 59650 Villeneuve–d’Ascq, FranceJoint Research Unit 1158, BioEcoAgro, Univ. Lille, INRAE, Univ. Liège, UPJV, JUNIA, Univ. Artois, Univ. Littoral Côte d’Opale, ICV—Institut Charles Viollette, 59650 Villeneuve–d’Ascq, FranceCenter for Infection and Immunity of Lille (CIIL), Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019—UMR 9017, 59000 Lille, FranceCenter for Infection and Immunity of Lille (CIIL), Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019—UMR 9017, 59000 Lille, FranceJoint Research Unit 1158, BioEcoAgro, Univ. Lille, INRAE, Univ. Liège, UPJV, JUNIA, Univ. Artois, Univ. Littoral Côte d’Opale, ICV—Institut Charles Viollette, 59650 Villeneuve–d’Ascq, FranceJoint Research Unit 1158, BioEcoAgro, Univ. Lille, INRAE, Univ. Liège, UPJV, JUNIA, Univ. Artois, Univ. Littoral Côte d’Opale, ICV—Institut Charles Viollette, 59650 Villeneuve–d’Ascq, FranceJoint Research Unit 1158, BioEcoAgro, Univ. Lille, INRAE, Univ. Liège, UPJV, JUNIA, Univ. Artois, Univ. Littoral Côte d’Opale, ICV—Institut Charles Viollette, 59650 Villeneuve–d’Ascq, FranceJoint Research Unit 1158, BioEcoAgro, Univ. Lille, INRAE, Univ. Liège, UPJV, JUNIA, Univ. Artois, Univ. Littoral Côte d’Opale, ICV—Institut Charles Viollette, 59650 Villeneuve–d’Ascq, FranceCenter for Infection and Immunity of Lille (CIIL), Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019—UMR 9017, 59000 Lille, FranceLaboratory of Aromatic and Medicinal Plants, Biotechnology Centre of Borj-Cedria (CBBC), Hammam-Lif 2050, TunisiaCenter for Infection and Immunity of Lille (CIIL), Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019—UMR 9017, 59000 Lille, FranceJoint Research Unit 1158, BioEcoAgro, Univ. Lille, INRAE, Univ. Liège, UPJV, JUNIA, Univ. Artois, Univ. Littoral Côte d’Opale, ICV—Institut Charles Viollette, 59650 Villeneuve–d’Ascq, FranceThe COVID-19 pandemic, caused by SARS-CoV-2, addressed the lack of specific antiviral drugs against coronaviruses. In this study, bioguided fractionation performed on both ethyl acetate and aqueous sub-extracts of <i>Juncus acutus</i> stems led to identifying luteolin as a highly active antiviral molecule against human coronavirus HCoV-229E. The apolar sub-extract (CH<sub>2</sub>Cl<sub>2</sub>) containing phenanthrene derivatives did not show antiviral activity against this coronavirus. Infection tests on Huh-7 cells, expressing or not the cellular protease TMPRSS2, using luciferase reporter virus HCoV-229E-Luc showed that luteolin exhibited a dose-dependent inhibition of infection. Respective IC<sub>50</sub> values of 1.77 µM and 1.95 µM were determined. Under its glycosylated form (luteolin-7-<i>O</i>-glucoside), luteolin was inactive against HCoV-229E. Time of addition assay showed that utmost anti-HCoV-229E activity of luteolin was achieved when added at the post-inoculation step, indicating that luteolin acts as an inhibitor of the replication step of HCoV-229E. Unfortunately, no obvious antiviral activity for luteolin was found against SARS-CoV-2 and MERS-CoV in this study. In conclusion, luteolin isolated from <i>Juncus acutus</i> is a new inhibitor of alphacoronavirus HCoV-229E.https://www.mdpi.com/1420-3049/28/11/4263HCoV-229ESARS-CoV-2MERS-CoV<i>Juncus</i> speciesbioguided fractionationluteolin
spellingShingle Asma Hakem
Lowiese Desmarets
Ramla Sahli
Rawen Ben Malek
Charline Camuzet
Nathan François
Gabriel Lefèvre
Jennifer Samaillie
Sophie Moureu
Sevser Sahpaz
Sandrine Belouzard
Riadh Ksouri
Karin Séron
Céline Rivière
Luteolin Isolated from <i>Juncus acutus</i> L., a Potential Remedy for Human Coronavirus 229E
Molecules
HCoV-229E
SARS-CoV-2
MERS-CoV
<i>Juncus</i> species
bioguided fractionation
luteolin
title Luteolin Isolated from <i>Juncus acutus</i> L., a Potential Remedy for Human Coronavirus 229E
title_full Luteolin Isolated from <i>Juncus acutus</i> L., a Potential Remedy for Human Coronavirus 229E
title_fullStr Luteolin Isolated from <i>Juncus acutus</i> L., a Potential Remedy for Human Coronavirus 229E
title_full_unstemmed Luteolin Isolated from <i>Juncus acutus</i> L., a Potential Remedy for Human Coronavirus 229E
title_short Luteolin Isolated from <i>Juncus acutus</i> L., a Potential Remedy for Human Coronavirus 229E
title_sort luteolin isolated from i juncus acutus i l a potential remedy for human coronavirus 229e
topic HCoV-229E
SARS-CoV-2
MERS-CoV
<i>Juncus</i> species
bioguided fractionation
luteolin
url https://www.mdpi.com/1420-3049/28/11/4263
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