New insights into the antiviral activity of nordihydroguaiaretic acid: Inhibition of dengue virus serotype 1 replication.

Autor: Martinez F; Universidad Nacional de Córdoba, Facultad de Ciencias Médicas, Instituto de Virología 'Dr. J. M. Vanella', Cdad. Universitaria, Córdoba X5000HUA, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina., Ghietto LM; Universidad Nacional de Córdoba, Facultad de Ciencias Médicas, Instituto de Virología 'Dr. J. M. Vanella', Cdad. Universitaria, Córdoba X5000HUA, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina., Lingua G; Universidad Nacional de Córdoba, Facultad de Ciencias Médicas, Instituto de Virología 'Dr. J. M. Vanella', Cdad. Universitaria, Córdoba X5000HUA, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina., Mugas ML; Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Ciencias Farmacéuticas, Farmacognosia. Haya de la Torre y Medina Allende, Ciudad Universitaria, Córdoba X5000HUA, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto Multidisciplinario de Biología Vegetal (IMBIV), Av. Vélez Sarsfield 1666. CP, Córdoba X5016GCN, Argentina., Aguilar JJ; Universidad Nacional de Córdoba, Facultad de Ciencias Médicas, Instituto de Virología 'Dr. J. M. Vanella', Cdad. Universitaria, Córdoba X5000HUA, Argentina., Gil P; Universidad Nacional de Córdoba, Facultad de Ciencias Médicas, Instituto de Virología 'Dr. J. M. Vanella', Cdad. Universitaria, Córdoba X5000HUA, Argentina., Pisano MB; Universidad Nacional de Córdoba, Facultad de Ciencias Médicas, Instituto de Virología 'Dr. J. M. Vanella', Cdad. Universitaria, Córdoba X5000HUA, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina., Marioni J; Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Ciencias Farmacéuticas, Farmacognosia. Haya de la Torre y Medina Allende, Ciudad Universitaria, Córdoba X5000HUA, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto Multidisciplinario de Biología Vegetal (IMBIV), Av. Vélez Sarsfield 1666. CP, Córdoba X5016GCN, Argentina., Paglini MG; Universidad Nacional de Córdoba, Facultad de Ciencias Médicas, Instituto de Virología 'Dr. J. M. Vanella', Cdad. Universitaria, Córdoba X5000HUA, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET-Universidad Nacional de Córdoba, Córdoba, Argentina., Contigiani MS; Universidad Nacional de Córdoba, Facultad de Ciencias Médicas, Instituto de Virología 'Dr. J. M. Vanella', Cdad. Universitaria, Córdoba X5000HUA, Argentina., Núñez-Montoya SC; Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Ciencias Farmacéuticas, Farmacognosia. Haya de la Torre y Medina Allende, Ciudad Universitaria, Córdoba X5000HUA, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto Multidisciplinario de Biología Vegetal (IMBIV), Av. Vélez Sarsfield 1666. CP, Córdoba X5016GCN, Argentina. Electronic address: sununez@unc.edu.ar., Konigheim BS; Universidad Nacional de Córdoba, Facultad de Ciencias Médicas, Instituto de Virología 'Dr. J. M. Vanella', Cdad. Universitaria, Córdoba X5000HUA, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina. Electronic address: brenda.konigheim@unc.edu.ar.
Jazyk: angličtina
Zdroj: Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2022 Nov; Vol. 106, pp. 154424. Date of Electronic Publication: 2022 Sep 02.
DOI: 10.1016/j.phymed.2022.154424
Abstrakt: Background: Dengue virus (DENV) is considered one of the most important pathogens in the world causing 390 million infections each year. Currently, the development of vaccines against DENV presents some shortcomings and there is no antiviral therapy available for its infection. An important challenge is that both treatments and vaccines must be effective against all four DENV serotypes. Nordihydroguaiaretic acid (NDGA), isolated from Larrea divaricata Cav. (Zygophyllaceae) has shown a significant inhibitory effect on a broad spectrum of viruses, including DENV serotypes 2 and 4.
Purpose: We evaluated the in vitro virucidal and antiviral activity of NDGA on DENV serotype 1 (DENV1), including the study of its mechanism of action, to provide more evidence on its antiviral activity.
Methods: The viability of viral particles was quantified by the plaque-forming unit reduction method. NDGA effects on DENV1 genome and viral proteins were evaluated by qPCR and immunofluorescence, respectively. Lysosomotropic activity was assayed using acridine orange and neutral red dyes.
Results: NDGA showed in vitro virucidal and antiviral activity against DENV1. The antiviral effect would be effective within the first 2 h after viral internalization, when the uncoating process takes place. In addition, we determined by qPCR that NDGA decreases the amount of intracellular RNA of DENV1 and, by immunofluorescence, the number of cells infected. These results indicate that the antiviral effect of NDGA would have an intracellular mechanism of action, which is consistent with its ability to be incorporated into host cells. Considering the inhibitory activity of NDGA on the cellular lipid metabolism, we compared the antiviral effect of two inhibitors acting on two different pathways of this type of metabolism: 1) resveratrol that inhibits the sterol regulatory element of binding proteins, and 2) caffeic acid that inhibits the 5-lipoxygenase (5-LOX) enzyme. Only caffeic acid produced an inhibitory effect on DENV1 infection. We studied the lysosomotropic activity of NDGA on host cells and found, for the first time, that this compound inhibited the acidification of cell vesicles which would prevent DENV1 uncoating process.
Conclusion: The present work contributes to the knowledge of NDGA activity on DENV. We describe its activity on DENV1, a serotype different to those that have been already reported. Moreover, we provide evidence on which stage/s of the viral replication cycle NDGA exerts its effects. We suggest that the mechanism of action of NDGA on DENV1 is related to its lysosomotropic effect, which inhibits the viral uncoating process.
Competing Interests: Declaration of Competing Interest All data were generated in-house, and no paper mill was used. All authors agree to be accountable for all aspects of work ensuring integrity and accuracy.”
(Copyright © 2022. Published by Elsevier GmbH.)
Databáze: MEDLINE
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