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Pomegranate Peel Extract as an Inhibitor of SARS-CoV-2 Spike Binding to Human ACE2 Receptor (in vitro): A Promising Source of Novel Antiviral Drugs.

ABSTRACT: Plant extracts are rich in bioactive compounds, such as polyphenols, sesquiterpenes, and triterpenes, which potentially have antiviral activities. As a consequence of the coronavirus disease 2019 pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus, thousands of scientists have been working tirelessly trying to understand the biology of this new virus and the disease pathophysiology, with the main goal of discovering effective preventive treatments and therapeutic agents. Plant-derived secondary metabolites may play key roles in preventing and counteracting the rapid spread of SARS-CoV-2 infections by inhibiting the activity of several viral proteins, in particular those involved in the virus entry into the host cells and its replication. Using in vitro approaches, we investigated the role of a pomegranate peel extract (PPE) in attenuating the interaction between the SARS-CoV-2 Spike glycoprotein and the human angiotensin-converting enzyme 2 receptor, and on the activity of the virus 3CL protease. Although further studies will be determinant to assess the efficacy of this extract in vivo, our results opened new promising opportunities to employ natural extracts for the development of effective and innovative therapies in the fight against SARS-CoV-2.

SUBMITTER: Tito A

PROVIDER: S-EPMC8114579 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Pomegranate Peel Extract as an Inhibitor of SARS-CoV-2 Spike Binding to Human ACE2 Receptor (in vitro): A Promising Source of Novel Antiviral Drugs

Project description:Plant extracts are rich in bioactive compounds, such as polyphenols, sesquiterpenes, and triterpenes, which potentially have antiviral activities. As a consequence of the coronavirus disease 2019 pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus, thousands of scientists have been working tirelessly trying to understand the biology of this new virus and the disease pathophysiology, with the main goal of discovering effective preventive treatments and therapeutic agents. Plant-derived secondary metabolites may play key roles in preventing and counteracting the rapid spread of SARS-CoV-2 infections by inhibiting the activity of several viral proteins, in particular those involved in the virus entry into the host cells and its replication. Using <i>in vitro</i> approaches, we investigated the role of a pomegranate peel extract (PPE) in attenuating the interaction between the SARS-CoV-2 Spike glycoprotein and the human angiotensin-converting enzyme 2 receptor, and on the activity of the virus 3CL protease. Although further studies will be determinant to assess the efficacy of this extract <i>in vivo</i>, our results opened new promising opportunities to employ natural extracts for the development of effective and innovative therapies in the fight against SARS-CoV-2.

2021-10-06 | MTBLS2309 | MetaboLights

Transcriptomic Analysis of Orange Fruit Treated with Pomegranate Peel Extract (PGE).

Project description:A Pomegranate Peel Extract (PGE) has been proposed as a natural antifungal substance with a wide range of activity against plant diseases. Previous studies showed that the extract has a direct antimicrobial activity and can elicit resistance responses in plant host tissues. In the present study, the transcriptomic response of orange fruit toward PGE treatments was evaluated. RNA-seq analyses, conducted on wounded fruits 0, 6, and 24 h after PGE applications, showed a significantly different transcriptome in treated oranges as compared to control samples. The majority (273) of the deferentially expressed genes (DEGs) were highly up-regulated compared to only 8 genes that were down-regulated. Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis showed the involvement of 1233 gene ontology (GO) terms and 35 KEGG metabolic pathways. Among these, important defense pathways were induced and antibiotic biosynthesis was the most enriched one. These findings may explain the underlying preventive and curative activity of PGE against plant diseases.

| S-EPMC6524005 | biostudies-literature

Pomegranate peel extract polyphenols attenuate the SARS-CoV-2 S-glycoprotein binding ability to ACE2 Receptor: In silico and in vitro studies.

Project description:The novel coronavirus disease (Covid-19) has become a major health threat globally. The interaction of SARS-CoV-2 spike (S) glycoprotein receptor-binding domain (RBD) with ACE2 receptor on host cells was recognized as the first step of virus infection and therefore as one of the primary targets for novel therapeutics. Pomegranate extracts are rich sources of bioactive polyphenols that were already recognized for their beneficial health effects. In this study, both in silico and in vitro methods were employed for evaluation of pomegranate peel extract (PoPEx), their major polyphenols, as well as their major metabolite urolithin A, to attenuate the contact of S-glycoprotein RBD and ACE2. Our results showed that PoPEx, punicalin, punicalagin and urolithin A exerted significant potential to block the S-glycoprotein-ACE2 contact. These in vitro results strongly confirm the in silico predictions and provide a valuable insight in the potential of pomegranate polyphenols for application in SARS-CoV-2 infection.

| S-EPMC8256661 | biostudies-literature

Antiviral drugs suppress infection of 2019-nCoV spike pseudotyped virus by interacting with ACE2 protein.

Project description:The outbreak of coronavirus disease 2019 (COVID-19) has induced a large number of deaths worldwide. Angiotensin-converting enzyme 2 (ACE2) is the entry receptor for the 2019 novel coronavirus (2019-nCoV) to infect the host cells. Therefore, ACE2 may be an important target for the prevention and treatment of COVID-19. The aim of this study was to investigate the inhibition effect of valaciclovir hydrochloride (VACV), zidovudine (ZDV), saquinavir (SQV), and efavirenz (EFV) on 2019-nCoV infection. The results of molecule docking and surface plasmon resonance showed that VACV, ZDV, SQV, and EFV could bind to ACE2 protein, with the KD value of (4.33 ± 0.09) e-8 , (6.29 ± 1.12) e-6 , (2.37 ± 0.59) e-5 , and (4.85 ± 1.57) e-5 M, respectively. But only ZDV and EFV prevent the 2019-nCoV spike pseudotyped virus to enter ACE2-HEK293T cells with an EC50 value of 4.30 ± 1.46 and 3.92 ± 1.36 μM, respectively. ZDV and EFV also have a synergistic effect on preventing entry of virus into cells. In conclusion, ZDV and EFV suppress 2019-nCoV infection of ACE2-HEK293T cells by interacting with ACE2.

| S-EPMC8646714 | biostudies-literature

Nutrient digestibility, hindgut metabolites and antioxidant status of dogs supplemented with pomegranate peel extract.

Project description:The present study assessed the effect of dietary supplementation of pomegranate peel (methanolic) extract (PPE) on the nutrient digestibility, faecal fermentative metabolites and antioxidant status of dogs. Six medium-sized dogs of mixed breeds were allocated to two groups in a replicated cross-over design and fed a basal diet with and without supplementation of PPE at 50 mg/kg body weight. Each of the experimental periods consisted of 30 d, with a 21 d washout period in between. Results indicated that PPE supplementation led to no significant changes in nutrient digestibility except a trend of improvement (P = 0·070) in crude fibre digestibility. PPE supplementation significantly (P < 0·001) influenced faecal pH, ammonia and lactate production, indicative of positive effects of PPE polyphenols. PPE supplementation further increased faecal SCFA concentration accompanied by a reduction (P < 0·01) in branched-chain fatty acids. PPE supplementation also improved (P < 0·05) indices of erythrocytic antioxidants, namely reduced glutathione, catalase, glutathione peroxidase and glutathione S-transferase together with an improvement in lipid peroxidation. Overall, it can be concluded that dietary supplementation with PPE at 50 mg/kg body weight had a positive impact on hindgut fermentation and antioxidant status in dogs, thereby demonstrating its potential as a gut health-promoting nutraceutical.

| S-EPMC5672305 | biostudies-literature

Pomegranate peel methanolic-extract improves the shelf-life of edible-oils under accelerated oxidation conditions.

Project description:Natural antioxidants extracted from agri-waste resources have gained increased economic, sustainable, and health attention due to their sustainability, safer food-applications, and beneficial components. Pomegranate peel extracts (Punica Granatum L.) have natural phytochemicals with superior protective effects stabilizing a variety of the most common vegetable oils consumed globally. Among five different pomegranate peel extracts, methanolic extract has maximum total phenolic content of 18.89%, a total flavonoid content of 13.95 mg QE kg-1, and a relative antioxidant activity of 93% when compared to other pomegranate peel extracts. Additionally, the HPLC analysis of pomegranate peel methanolic extract exhibited the maximum number of phenolic and flavonoid fractions. HPLC fractions showed that pyrogallol and ellagic acids were the most abundant phenolic compounds with 453 and 126 mg kg-1, respectively. In terms of flavonoid fractions, hesperidine and quercetrin were the highest detected-flavonoids with about 50 and 35 mg kg-1, respectively, from HPLC flavonoids fractions. Therefore, pomegranate peel methanolic extract was selected at different concentrations (100, 200, 400, and 600 ppm) for the stabilizing experiment of Egyptian freshly refined edible oils (sunflower, soybean, and corn oils) in comparison with synthetic antioxidant (tert-butyl hydroquinone TBHQ-200 ppm) during accelerated storage at 70°C for 10 days. The results from the accelerated storage experiment indicated that pomegranate peel methanolic extract (at different concentrations: 200, 400, and 600 ppm) exhibited stronger antioxidant capability in all tested oils rather than negative controls (without antioxidant) and synthetic antioxidant TBHQ-200. Under accelerated oxidation conditions, pomegranate peel methanolic extract have the potential capability to improve the shelf life of edible oils in comparison with the most powerful synthetic antioxidant (TBHQ-200 ppm).

| S-EPMC7174205 | biostudies-literature

Pomegranate peel extract ameliorates the severity of experimental autoimmune encephalomyelitis via modulation of gut microbiota.

Project description:Multiple sclerosis (MS) is a CNS autoimmune disease characterized by demyelination and inflammatory infiltration with a high disability rate. Increasing evidence has demonstrated the importance of gut microbiota as an environmental risk factor in MS and its animal model experimental autoimmune encephalomyelitis (EAE). Diet is the main determinant of gut microbiota composition and function, which greatly affects the shaping of microbial structure. Pomegranate peel, a waste product in the production of juice, is rich in health-promoting compounds. However, its individual constituents, immunoregulatory activities, and action associated with bacterial diversity in the gut microbiota are largely unknown. Here, the main nutrient ingredients of pomegranate peel extract (PPE) were identified as phenols, flavonoids, amino acids, carbohydrates, fatty acids, lipids, nucleotides, organic acids, alcohols, and vitamins via metabolomics evaluation. We found, for the first time, oral PPE (100 mg/kg/day) not only effectively relieves EAE, inhibits CNS inflammatory factor infiltration and myelin loss, but also reshapes gut microbiota. Furthermore, recipient EAE mice with fecal transplantation from the PPE-treated donor delayed the disease development significantly. 16S rRNA gene sequencing revealed the increased gut microbiota richness in PPE-treated group. Among them, Lactobacillaceae enriched significantly, while Alcaligenaceae and Acidaminococcacea decreased remarkably. In conclusion, our data demonstrated that gut microbiota mediated the beneficial effects of oral PPE on EAE, and provided new ideas for developing the prebiotic value of pomegranate peel for the treatment of autoimmune diseases.

| S-EPMC7751635 | biostudies-literature

Computational study of pomegranate peel extract polyphenols as potential inhibitors of SARS-CoV-2 virus internalization.

Project description:The search for effective coronavirus disease (COVID-19) therapy has attracted a great deal of scientific interest due to its unprecedented health care system overload worldwide. We have carried out a study to investigate the in silico effects of the most abundant pomegranate peel extract constituents on the multi-step process of serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) internalization in the host cells. Binding affinities and interactions of ellagic acid, gallic acid, punicalagin and punicalin were studied on four selected protein targets with a significant and confirmed role in the process of the entry of virus into a host cell. The protein targets used in this study were: SARS-CoV-2 spike glycoprotein, angiotensin-converting enzyme 2, furin and transmembrane serine protease 2. The results showed that the constituents of pomegranate peel extracts, namely punicalagin and punicalin had very promising potential for significant interactions with the selected protein targets and were therefore deemed good candidates for further in vitro and in vivo evaluation.

| S-EPMC7668668 | biostudies-literature

Anti-Inflammatory Effects of Pomegranate Peel Extract in THP-1 Cells Exposed to Particulate Matter PM10.

Project description:Epidemiological and experimental evidence support health risks associated with the exposure to airborne particulate matter with a diameter of <10??M (PM10). PM10 stimulates the production of reactive oxygen species (ROS) and inflammatory mediators. Thus, we assumed that natural antioxidants might provide health benefits attenuating hazardous effects of PM10. In the present study, we examined the effects of pomegranate peel extract (PPE) on THP-1 monocytic cells exposed to PM10. PM10 induced cytotoxicity and the production of ROS. It also increased the expression and secretion of inflammatory cytokines, such as tumor necrosis factor-? (TNF-?), interleukin-1? (IL-1?), and monocyte chemoattractant protein-1 (MCP-1), and cell adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). PPE at 10-100??g?mL(-1) attenuated the production of ROS and the expression of TNF-?, IL-1?, MCP-1, and ICAM-1, but not VCAM-1, in THP-1 cells stimulated by PM10 (100??g?mL(-1)). PPE also attenuated the adhesion of PM10-stimulated THP-1 cells to EA.hy926 endothelial cells. PPE constituents, punicalagin and ellagic acid, attenuated PM10-induced monocyte adhesion to endothelial cells, and punicalagin was less cytotoxic compared to ellagic acid. The present study suggests that PPE and punicalagin may be useful in alleviating inflammatory reactions due to particulate matter.

| S-EPMC4877489 | biostudies-literature

Eco-Sustainable Silk Fibroin/Pomegranate Peel Extract Film as an Innovative Green Material for Skin Repair

Project description:Skin disorders are widespread around the world, affecting people of all ages, and oxidative stress represents one of the main causes of alteration in the normal physiological parameters of skin cells. In this work, we combined a natural protein, fibroin, with antioxidant compounds extracted in water from pomegranate waste. We demonstrate the effective and facile fabrication of bioactive and eco-sustainable films of potential interest for skin repair. The blended films are visually transparent (around 90%); flexible; stable in physiological conditions and in the presence of trypsin for 12 days; able to release the bioactive compounds in a controlled manner; based on Fickian diffusion; and biocompatible towards the main skin cells, keratinocytes and fibroblasts. Furthermore, reactive oxygen species (ROS) production tests demonstrated the high capacity of our films to reduce the oxidative stress induced in cells, which is responsible for various skin diseases.

| S-EPMC9224408 | biostudies-literature

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