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

AbstractZika 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.

Download Full-text

The P-MAPA immunomodulator partially prevents apoptosis induced by Zika virus infection in THP-1 cells

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666200602140005 ◽

2020 ◽

Vol 21 ◽

Cited By ~ 1

Author(s):

Morganna C. Lima ◽

Elisa A. N. Azevedo ◽

Clarice N. L. de Morais ◽

Larissa I. O. de Sousa ◽

Bruno M. Carvalho ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Death ◽

Virus Infection ◽

Virus Replication ◽

Zika Virus ◽

Mammalian Cells ◽

Caspase 3 ◽

Neurological Complications ◽

Zika Virus Infection

Background: Zika virus is an emerging arbovirus of global importance. ZIKV infection is associated with a range of neurological complications such as the Congenital Zika Syndrome and Guillain Barré Syndrome. Despite the magnitude of recent outbreaks, there is no specific therapy to prevent or to alleviate disease pathology. Objective: To investigate the role of P-MAPA immunomodulator in Zika-infected THP-1 cells. Methods: THP-1 cells were subjected at Zika virus infection (Multiplicity of Infection = 0.5) followed by treatment with P-MAPA for until 96 hours post-infection. After that, the cell death was analyzed by annexin+/ PI+ and caspase 3/ 7+ staining by flow cytometry. In addition, the virus replication and cell proliferation were accessed by RT-qPCR and Ki67 staining, respectively. Results: We demonstrate that P-MAPA in vitro treatment significantly reduces Zika virus-induced cell death and caspase-3/7 activation on THP-1 infected cells, albeit it has no role in virus replication and cell proliferation. Conclusions: Our study reveals that P-MAPA seems to be a satisfactory alternative to inhibits the effects of Zika virus infection in mammalian cells.

Download Full-text

JMX0207, a Niclosamide Derivative with Improved Pharmacokinetics, Suppresses Zika Virus Infection Both In Vitro and In Vivo

ACS Infectious Diseases ◽

10.1021/acsinfecdis.0c00217 ◽

2020 ◽

Vol 6 (10) ◽

pp. 2616-2628 ◽

Cited By ~ 1

Author(s):

Zhong Li ◽

Jimin Xu ◽

Yuekun Lang ◽

Xiaoyu Fan ◽

Lili Kuo ◽

...

Keyword(s):

Virus Infection ◽

Zika Virus ◽

Zika Virus Infection

Download Full-text

MAIT cells are activated in acute Dengue virus infection and after in vitro Zika virus infection

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0006154 ◽

2018 ◽

Vol 12 (1) ◽

pp. e0006154 ◽

Cited By ~ 21

Author(s):

Dominic Paquin-Proulx ◽

Vivian I. Avelino-Silva ◽

Bianca A. N. Santos ◽

Nathália Silveira Barsotti ◽

Fabiana Siroma ◽

...

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Zika Virus ◽

Dengue Virus Infection ◽

Mait Cells ◽

Zika Virus Infection

Download Full-text

Synergistic in-vitro antiviral effects of combination treatment using anidulafungin and T-1105 against Zika virus infection

Antiviral Research ◽

10.1016/j.antiviral.2021.105188 ◽

2021 ◽

pp. 105188

Author(s):

Jeng-Wei Lu ◽

Yen-Chen Chen ◽

Chin-Kai Huang ◽

Kuan-Chih Lin ◽

Yi-Jung Ho

Keyword(s):

Virus Infection ◽

Combination Treatment ◽

Zika Virus ◽

Antiviral Effects ◽

Zika Virus Infection

Download Full-text

Beneficial in vitro effects of the passion fruit seed extract against placental Zika virus infection

Placenta ◽

10.1016/j.placenta.2021.07.136 ◽

2021 ◽

Vol 112 ◽

pp. e42

Author(s):

Eloiza Tanabe ◽

Jaqueline Santos ◽

Keyla Pires ◽

Monique Nova ◽

Karen Borbely ◽

...

Keyword(s):

Virus Infection ◽

Zika Virus ◽

Seed Extract ◽

Passion Fruit ◽

Zika Virus Infection ◽

In Vitro Effects

Download Full-text

Autopsy and Postmortem Studies Are Concordant: Pathology of Zika Virus Infection Is Neurotropic in Fetuses and Infants With Microcephaly Following Transplacental Transmission

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2016-0343-oa ◽

2016 ◽

Vol 141 (1) ◽

pp. 68-72 ◽

Cited By ~ 43

Author(s):

David A. Schwartz

Keyword(s):

Virus Infection ◽

Brain Damage ◽

Vertical Transmission ◽

Zika Virus ◽

In Vivo Studies ◽

Cytopathic Effects ◽

Zika Virus Infection ◽

Postmortem Studies

Context.—Pathology studies have been important in concluding that Zika virus infection occurring in pregnant women can result in vertical transmission of the agent from mother to fetus. Fetal and infant autopsies have provided crucial direct evidence that Zika virus can infect an unborn child, resulting in microcephaly, other malformations, and, in some cases, death. Objective.—To better understand the etiologic role and mechanism(s) of Zika virus in causing birth defects such as microcephaly, this communication analyzes the spectrum of clinical and autopsy studies reported from fetuses and infants who developed intrauterine Zika virus infection, and compares these findings with experimental data related to Zika virus infection. Design.—Retrospective analysis of reported clinical, autopsy, pathology, and related postmortem studies from 9 fetuses and infants with intrauterine Zika virus infection and microcephaly. Results.—All fetuses and infants examined demonstrated an overlapping spectrum of gross and microscopic neuropathologic abnormalities. Direct cytopathic effects of infection by the Zika virus were confined to the brain; in cases where other organs were evaluated, no direct viral effects were identified. Conclusions.—There is concordance of the spectrum of brain damage, reinforcing previous data indicating that the Zika virus has a strong predilection for cells of the fetal central nervous system following vertical transmission. The occurrence of additional congenital abnormalities suggests that intrauterine brain damage from Zika virus interferes with normal fetal development, resulting in fetal akinesia. Experimental in vitro and in vivo studies of Zika virus infection corroborate the human autopsy findings of neural specificity.

Download Full-text