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

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.

In Vitro Anti-HIV-1 Reverse Transcriptase and Integrase Properties of Punica granatum L. Leaves, Bark, and Peel Extracts and Their Main Compounds

“…In addition to the hydrolyzable tannins identified in fruit peel, bark contains C-glycosidic ellagitannins, such as punicacorteins A-D, punigluconin, casuariin, and casuariniin [11], and dimeric gallic acid glycosides [12]. Leaves contain many gallic acid derivatives, also known as gallotannins and ellagitannins [3,13], and phenolics and flavone glycosides [3,14]. Both qualitative and quantitative differences have been observed in different pomegranate cultivars [9,15] as well as seasonal changes in their content [16].…”

“…Due to its bioactive compounds, pomegranate possesses antioxidant, anti-inflammatory, antidiabetic, anticancer, antimicrobial, cardioprotective, and neuroprotective effects [1,5,6,[17][18][19][20][21]. Antiviral properties against human herpes virus 3 (HHV-3) [22], herpes simplex virus 2 (HSV-2) [23], influenza virus [24], and enterovirus 71 [25] have been reported and, recently, Acquadro et al 2020 [14] tested the extract of pomegranate leaves from Sardinia for its antiviral properties against Zika virus. Moreover, pomegranate fruit juice contains molecules that target the virus envelope and are able to prevent HIV-1 binding to the cellular receptor CD4 and CXCR4/CCR5 [26].…”

Medicinal Plants Against Coronavirus (SARS-COV-2) in Morocco Via Computational Virtual Screening Approach

“…Regarding antiviral activity, ellagic acid had an IC50 value of 1.4 µM and 6.4 µM against Ebola virus (EBOV) and Marburg virus (MARV) pseudovirions, respectively (Cui et al, 2018). In addition, its anti-Zika activities and antihuman rhinoviruses (anti-HRV) activities have been demonstrated (Acquadro et al, 2020;Park, Kwon, Yoo, Choiand Ahn, 2014).…”

Variation of the Polyphenolic Composition and Antioxidant Capacity of Freshly Prepared Pomegranate Leaf Infusions over One-Day Storage

“…Recent studies already demonstrated that PL extracts possessed superior AOA, owing to the various flavonoids and tannins, among others, which are associated with many biological properties, including anti-inflammation, anti-microbial, anti-diabetes, anti-virus, anti-diarrheal, anti-ulcer, and hepato- and nephron- protection [ 11 , 13 , 16 , 25 , 26 , 55 , 56 , 57 ]. Nonetheless, only a few works have studied the relationship between the health-promoting effects and a certain compound isolated from PL extracts; there were scarcely any articles about PLI that illustrated the changing features between AOA and polyphenolic composition.…”