Punica granatum Leaf Ethanolic Extract and Ellagic Acid as Inhibitors of Zika Virus Infection

Stefano Acquadro; Andrea Civra; Cecilia Cagliero; Arianna Marengo; Massimo Rittà; Rachele Francese; Cinzia Sanna; Cinzia Bertea; Barbara Sgorbini; David Lembo; Manuela Donalisio; Patrizia Rubiolo

doi:10.1055/a-1232-5705

Planta Medica, Inhaltsverzeichnis

Planta Med 2020; 86(18): 1363-1374
DOI: 10.1055/a-1232-5705

Biological and Pharmacological Activity

Original Papers

Punica granatum Leaf Ethanolic Extract and Ellagic Acid as Inhibitors of Zika Virus Infection

Stefano Acquadro‡

¹Department of Drug Science and Technology, University of Turin, Turin, Italy

,

Andrea Civra‡

²Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy

,

Cecilia Cagliero

¹Department of Drug Science and Technology, University of Turin, Turin, Italy

,

Arianna Marengo

¹Department of Drug Science and Technology, University of Turin, Turin, Italy

,

Massimo Rittà

²Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy

,

Rachele Francese

²Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy

,

Cinzia Sanna

³Department of Environmental and Life Sciences University of Cagliari, Cagliari, Italy

,

Cinzia Bertea

⁴Department of Life Sciences and Systems Biology, University of Turin, Turin, Italy

,

Barbara Sgorbini

¹Department of Drug Science and Technology, University of Turin, Turin, Italy

,

David Lembo

²Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy

,

Manuela Donalisio

²Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy

,

Patrizia Rubiolo

¹Department of Drug Science and Technology, University of Turin, Turin, Italy

› Institutsangaben

Abstract

Zika virus, an arthropod-borne flavivirus, is an emerging healthcare threat worldwide. Zika virus is responsible for severe neurological effects, such as paralytic Guillain-Barrè syndrome, in adults, and also congenital malformations, especially microcephaly. No specific antiviral drugs and vaccines are currently available, and treatments are palliative, but medicinal plants show great potential as natural sources of anti-Zika phytochemicals. This study deals with the investigation of the composition, cytotoxicity, and anti-Zika activity of Punica granatum leaf ethanolic extract, fractions, and phytoconstituents. P. granatum leaves were collected from different areas in Italy and Greece in different seasons. Crude extracts were analyzed and fractionated, and the pure compounds were isolated. The phytochemical and biomolecular fingerprint of the pomegranate leaves was determined. The antiviral activities of the leaf extract, fractions, and compounds were investigated against the MR766 and HPF2013 Zika virus strains in vitro. Both the extract and its fractions were found to be active against Zika virus infection. Of the compounds isolated, ellagic acid showed particular anti-Zika activities, with EC₅₀ values of 30.86 µM for MR766 and 46.23 µM for HPF2013. The mechanism of action was investigated using specific antiviral assays, and it was demonstrated that ellagic acid was primarily active as it prevented Zika virus infection and was able to significantly reduce Zika virus progeny production. Our data demonstrate the anti-Zika activity of pomegranate leaf extract and ellagic acid for the first time. These findings identify ellagic acid as a possible anti-Zika candidate compound that can be used for preventive and therapeutic interventions.

Key words

Zika virus - Punica granatum - Lythraceae - leaf ethanolic extract - phytochemical and biomolecular fingerprint - antiviral - ellagic acid

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Referenzen

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