The citrus flavanone naringenin impairs dengue virus replication in human cells

Abstract

Dengue is one of the most significant health problems in tropical and sub-tropical regions throughout the world. Nearly 390 million cases are reported each year. Although a vaccine was recently approved in certain countries, an anti-dengue virus drug is still needed. Fruits and vegetables may be sources of compounds with medicinal properties, such as flavonoids. This study demonstrates the anti-dengue virus activity of the citrus flavanone naringenin, a class of flavonoid. Naringenin prevented infection with four dengue virus serotypes in Huh7.5 cells. Additionally, experiments employing subgenomic RepDV-1 and RepDV-3 replicon systems confirmed the ability of naringenin to inhibit dengue virus replication. Antiviral activity was observed even when naringenin was used to treat Huh7.5 cells 24 h after dengue virus exposure. Finally, naringenin anti-dengue virus activity was demonstrated in primary human monocytes infected with dengue virus sertoype-4, supporting the potential use of naringenin to control dengue virus replication. In conclusion, naringenin is a suitable candidate molecule for the development of specific dengue virus treatments.

Comprehensive characterisation of polyphenols in leaves and stems of three anti‐dengue virus type‐2 active Brazilian Faramea species (Rubiaceae) by HPLC‐DAD‐ESI‐MS/MS

“…Several classes of flavonoids have been reported to present dengue antiviral activity specially flavanones, flavones and flavonols . The flavanone ( 27 ), previously isolated by us from the leaves of these three Faramea spp., showed a dose‐dependent reduction in viral load (IC 50 = 13.1 μg/mL) and the ability to control DENV‐2 replication .…”

“…However, by a bioassay guided fractionation, the flavanones ( 6 and 13 ), as well as the flavonols ( 9 and 26 ) were previously isolated from the leaves of F. hyacinthina and/or F. truncata from non‐cytotoxic but non‐cytoprotective fractions . In addition, the flavanone naringenin ( 28 ), present in the leaves of all three species in a small amount, showed anti‐DENV activity with four DENV serotypes in Huh7.5 cells . Other flavonoids characterised in these Faramea species have no significant antiviral activity against DENV‐2 or their activity was not described.…”

“…12,13 Several classes of flavonoids have been reported to present dengue antiviral activity specially flavanones, flavones and flavonols. 6,7,[45][46][47][48][49] The flavanone (27), previously isolated by us from the leaves of these three Faramea spp., showed a dose-dependent reduction in viral load (IC 50 = 13.1 μg/mL) and the ability to control DENV-2 replication. 13 However, by a bioassay guided fractionation, the flavanones (6 and 13), as well as the flavonols (9 and 26) were previously isolated from the leaves of F. hyacinthina and/or F. truncata from non-cytotoxic but non-cytoprotective fractions.…”

Characteristics of flavonoids as potent MERS‐CoV 3C‐like protease inhibitors

“…With a synthetic peptide with the FRET pair, a flavonoid library was screened to search MERS-CoV 3CLpro inhibitory compounds. Recent studies showed that some flavonoids have antiviral activity in some viruses (Frabasile et al, 2017;Jucá et al,2018;Kiat et al, 2006;Yang, Lin, Zhou, Liu, & Zhu, 2017;Zakaryan, Arabyan, Oo, & Zandi, 2017). Therefore, we assayed flavonoids and tried to induce their structural property crucial to bind with MERS-CoV 3CLpro.…”

Viral replicons as valuable tools for drug discovery

“…Dengue replicon systems have been successfully used for hit discovery by Lu et al, who identified phthalazinone derivatives as potent inhibitors of DENV2 replication [47]. Frabasile et al, using a similar screen, showed that naringenin, a citrus flavonone, greatly impaired genome replication using human Huh7.5 cells harbouring DENV1 and DENV3 replicons [48]. Hernandez-Morales et al tested a HCV compound library in a high-throughput DENV2 replicon screening assay, identifying JNJ-1A as an effective lead [49].…”