Abstract
The mosquito-borne viruses dengue (DENV) and Zika (ZIKV) viruses are two medically important pathogens in tropical and subtropical regions of the world. There is an urgent need of therapeutics against DENV and ZIKV, and medicinal plants are considered as a promising source of antiviral bioactive metabolites. In the present study, we evaluated the ability of Phyllanthus phillyreifolius, an endemic medicinal plant from Reunion Island, to prevent DENV and ZIKV infection in human cells. At non-cytotoxic concentration in vitro, incubation of infected A549 cells with a P. phillyreifolius extract or its major active phytochemical geraniin resulted in a dramatic reduction of virus progeny production for ZIKV as well as four serotypes of DENV. Virological assays showed that P. phillyreifolius extract-mediated virus inhibition relates to a blockade in internalization of virus particles into the host cell. Infectivity studies on ZIKV showed that both P. phillyreifolius and geraniin cause a loss of infectivity of the viral particles. Using a zebrafish model, we demonstrated that administration of P. phillyreifolius and geraniin has no effect on zebrafish locomotor activity while no morbidity nor mortality was observed up to 5 days post-inoculation. Thus, P. phillyreifolius could act as an important source of plant metabolite geraniin which is a promising antiviral compound in the fight against DENV and ZIKV.
Highlights
Mosquito-borne dengue (DENV) and Zika (ZIKV) viruses belonging to the flavivirus genus (Flaviviridae family) are two major concerns in public health worldwide [1]
We propose that antiviral action of P. phillyreifolius extract relates to its major compound geraniin which acts as a potent flavivirus inhibitor at the doses displaying no acute toxicity effects on zebrafish and without modifying its locomotor activity that could constitute a sign of stress
ZIKV and DENV Are Inhibited by an Ethanolic Extract of Phyllanthus phillyreifolius
Summary
Mosquito-borne dengue (DENV) and Zika (ZIKV) viruses belonging to the flavivirus genus (Flaviviridae family) are two major concerns in public health worldwide [1]. The geographic range of DENV spreads from tropical to subtropical regions [2,3]. Most hyperendemic regions are located in Southeast Asia and Latin America where severe outbreaks of dengue disease occur annually. Molecules 2020, 25, 2316 serotypes of DENV (DENV-1 to DENV-4) can cause clinical symptoms ranging from dengue fever to a severe form of disease with hemorrhage causing severe shock impairing patient vital prognosis [2]. No antiviral therapy is available for DENV infection, and prophylatic strategies are needed to prevent severe forms of dengue disease. ZIKV has become a major public health issue in the last decade [4,5]
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