The in vitro and in vivo antiviral properties of combined monoterpene alcohols against West Nile virus infection

Abstract

West Nile Virus (WNV) is a mosquito-borne flavivirus that can cause neuroinvasive disease in humans and animals for which no therapies are currently available. We studied an established combination of monoterpene alcohols (CMA) derived from Melaleuca alternifolia, against WNV infection. The in vitro results show that CMA exhibits virucidal activity, as well as reduces the viral titres and percentage of infected cells. The antiviral mechanism of action of CMA was studied. We found that CMA did not alter the intracellular pH, neither induced apoptosis, but did induce cell cycle arrest in the G0/G1-phase although that was not the antiviral mechanism. Furthermore, we tested CMA in vivo using IRF 3(-)(/)(-)/7(-/-)mice and it was found that CMA treatment significantly delayed morbidity due to WNV infection, reduced the loss of body weight and reduced the viral titres in brain. These findings suggest that CMA could be a therapeutic agent against WNV infection.

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“…The sesquiterpene hydrocarbon fraction, rather than the oxygenated fraction, accounted for the antiviral action against the Herpes Simplex-2 virus, an enveloped human pathogenic virus [ 47 ]. Furthermore, a mixture containing monoterpene alcohols and sesquiterpene hydrocarbons derived from Melaleuca alternifolia, showed promising in vivo antiviral efficacy against West Nile virus, an enveloped virus similar in structure to DENV [ 48 ].…”

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“…Recognizing these similarities and differences in the protein expression levels in response to ZIKV infection in both U251 and Vero cells are very important and relevant. Since the Vero cell line still is the most commonly used cell line to test a number of antiviral drugs, it is crucial to understand how well the proteomic profile of ZIKV infection in U251 cells, which is a more physiologically relevant cell type, compares to that in the Vero cell type (Perera et al, 2008; Farias et al, 2013; Zamora et al, 2016; Wang S. B et al, 2017; Haviernik et al, 2018). This way, eventual translation of the large number of antiviral drugs and vaccines that have already been tested in Vero cells against a number of other flaviviruses like Dengue Virus Type 2 and West Nile Virus, into the ZIKV system can be made more efficiently (Perera et al, 2008; Farias et al, 2013; Zamora et al, 2016).…”