Article ; Online: Quassinoids from Eurycoma longifolia with antiviral activities by inhibiting dengue virus replication.
Phytomedicine : international journal of phytotherapy and phytopharmacology
2023 Volume 110, Page(s) 154650
Abstract: Background: Dengue caused by dengue virus (DENV) spreads rapidly around the world. However, there are no worldwide licensed vaccines or specific antivirals to combat DENV infection. Quassinoids are the most characteristic components of Eurycoma ... ...
| Abstract | Background: Dengue caused by dengue virus (DENV) spreads rapidly around the world. However, there are no worldwide licensed vaccines or specific antivirals to combat DENV infection. Quassinoids are the most characteristic components of Eurycoma longifolia, which have been reported to display a variety of biological activities. However, whether quassinoids exert anti-DENV activities remains unknown. Purpose: To test the quassinoids of E. longifolia for their activity against DENV and to clarify the potential mechanisms. Methods: The quassinoids from E. longifolia were isolated by chromatography techniques, and their chemical structures were elucidated by spectroscopic analysis. The anti-DENV activities of quassinoids on baby hamster kidney cells BHK-21 were determined by lactate dehydrogenase (LDH) assay. The synthesis of progeny virus was measured by plaque assay. The expression levels of envelope protein (E) and non-structural protein 1 (NS1) were evaluated by qRT-PCR, Western blot and immunofluorescence assays. Molecular docking was used to screen the potential targets of the most active quassinoid against DENV-2, and surface plasmon resonance analysis was employed to confirm the direct binding between the most active quassinoid and potential target. Results: Twenty-four quassinoids, including three new quassinoids (1 - 3), were isolated from the ethanol extract of E. longifolia. Quassinoids 4, 5, 9, 11, 12, 15, 16, 17, 19 and 20 significantly reduced the LDH release at the stages of viral binding and entry or intracellular replication. Among them, 19 (6α-hydroxyeurycomalactone, 6α-HEL) exhibited the best anti-DENV-2 activities with an EC Conclusion: Ten quassinoids from E. longifolia showed anti-DENV activities at processes of virus binding and entry or intracellular replication. The most active quassinoid 6α-HEL exerts the anti-DENV-2 activities at intracellular replication stage by directly targeting the NS5-RdRp protein. These results suggest that 6α-HEL could be a promising candidate for the treatment of DENV-2 infection. |
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| MeSH term(s) | Animals ; Cricetinae ; Humans ; Antiviral Agents/chemistry ; Antiviral Agents/isolation & purification ; Antiviral Agents/pharmacology ; Dengue/drug therapy ; Eurycoma/chemistry ; Molecular Docking Simulation ; Quassins/isolation & purification ; Quassins/pharmacology ; RNA-Dependent RNA Polymerase ; Virus Replication/drug effects ; Dengue Virus/drug effects |
| Chemical Substances | Antiviral Agents ; Quassins ; RNA-Dependent RNA Polymerase (EC 2.7.7.48) |
| Language | English |
| Publishing date | 2023-01-05 |
| Publishing country | Germany |
| Document type | Journal Article |
| ZDB-ID | 1205240-1 |
| ISSN | 1618-095X ; 0944-7113 |
| ISSN (online) | 1618-095X |
| ISSN | 0944-7113 |
| DOI | 10.1016/j.phymed.2023.154650 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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