Ayapana triplinervis Essential Oil and Its Main Component Thymohydroquinone Dimethyl Ether Inhibit Zika Virus at Doses Devoid of Toxicity in Zebrafish

Abstract

Zika virus (ZIKV) is an emerging mosquito-borne virus of medical concern. ZIKV infection may represent a serious disease, causing neonatal microcephaly and neurological disorders. Nowadays, there is no approved antiviral against ZIKV. Several indigenous or endemic medicinal plants from Mascarene archipelago in Indian Ocean have been found able to inhibit ZIKV infection. The purpose of our study was to determine whether essential oil (EO) from Reunion Island medicinal plant Ayapana triplinervis, whose thymohydroquinone dimethyl ether (THQ) is the main component has the potential to prevent ZIKV infection in human cells. Virological assays were performed on human epithelial A549 cells infected with either GFP reporter ZIKV or epidemic viral strain. Zebrafish assay was employed to evaluate the acute toxicity of THQ in vivo. We showed that both EO and THQ inhibit ZIKV infection in human cells with IC50 values of 38 and 45 µg/mL, respectively. At the noncytotoxic concentrations, EO and THQ reduced virus progeny production by 3-log. Time-of-drug-addition assays revealed that THQ could act as viral entry inhibitor. At the antiviral effective concentration, THQ injection in zebrafish does not lead to any signs of stress and does not impact fish survival, demonstrating the absence of acute toxicity for THQ. From our data, we propose that THQ is a new potent antiviral phytocompound against ZIKV, supporting the potential use of medicinal plants from Reunion Island as a source of natural and safe antiviral substances against medically important mosquito-borne viruses.

Chemical Characteristics and Anticancer Activity of Essential Oil from Arnica Montana L. Rhizomes and Roots

“…The study on the use of 2.5-dimethoxy-p-cymene has demonstrated that this molecule isolated from A. triplinervis EO is a potent inhibitor of ZIKV infection in human cells. Moreover, assessment of the biosafety of 2.5-dimethoxy-p-cymene extracted from A. triplinervis has shown that injection of this molecule in zebrafish does not lead to any signs of stress and does not affect fish survival, demonstrating the absence of acute toxicity of this compound [46]. However, different results were obtained by Unnikrishnan et al [45].…”

“…Similarly, EOs of Arnica flower heads from different European populations have shown their chemical polymorphism [8,9,15,18,21]. However, very interesting is the fact that the proportion of the main EO components from the Arnica rhizomes and roots, i.e., 2,5-dimethoxy-p-cymene and thymol methyl ether, is similar to the chemical oil profile in such species as Ayapana triplinervis [44][45][46].…”

“…Conventional cancer therapies cause serious side effects [28]. However, many alternative treatments and therapies based on plants have been explored in the recent years, which is especially important for patients that do not tolerate extreme side effects [46]. Plants have been analyzed to identify their anticancer properties and characterized chemically to reveal the presence of many bioactive compounds [29,30].…”

“…2,5-dimethoxy-p-cymene, thymol methyl ether, p-methoxyheptanophenone, and 2,6-diisopropylanisole are the main components of the EOs in the underground parts of mountain Arnica. In view of continuation of the study, it is highly promising that the medicinal plant A. triplinervis from the family Asteraceae has recently been identified for the first time as a new source of antiviral phytocompounds targeting the entry of viral pathogens to cells, with 2.5-dimethoxy-p-cymene as the main component of EO extracted from leaves [46]. The study on the use of 2.5-dimethoxy-p-cymene has demonstrated that this molecule isolated from A. triplinervis EO is a potent inhibitor of ZIKV infection in human cells.…”

Monoterpenes and Their Derivatives—Recent Development in Biological and Medical Applications

“…The results demonstrated that both EO and THQ inhibit ZIKV infection in human cells with IC 50 values of 38 and 45 μM. It was noted that the inoculation of THQ at the antiviral effective concentration does not lead to any stress and does not impact fish survival [ 54 ].…”