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1,2,3,4,6-Pentagalloyl glucose of Pistacia lentiscus can inhibit the replication and transcription processes and viral pathogenesis of SARS-COV-2.

ABSTRACT: SARS-COV-2 stands as the source of the most catastrophic pandemic of this century, known as COVID-19. In this regard, we explored the effects of five Pistacia sp. active ingredients on the most crucial targets of SARS-COV-2, including 3CLpro, PLpro, RdRp, helicase, NSP15, and E protein. The results of molecular docking determined 1,2,3,4,6-pentagalloyl glucose (PG) as the most effective compound of Pistacia sp, which also confirmed its excellent binding affinities and stable interactions with helicase (-10.76 kcal/mol), RdRp (-10.19 kcal/mol), E protein (-9.51 kcal/mol), and 3CLpro (-9.47 kcal/mol). Furthermore, MD simulation was conducted to investigate the stability of all complexes throughout a 100 ns. In contrast to PLpro and NSP15, the analyses of Lennard-Jones potential, RMSDas, PCA, and SASA verified the ability of PG in forming stable and adequate interactions with RdRp, helicase, 3CLpro, and E protein due to standing as an effective inhibitor among the six targets, these data proposed the capability of PG, the most important compound of Pistacia sp., in inducing antiviral, anti-inflammatory, and antioxidant impacts on RdRp, helicase, 3CLpro, and E protein. Therefore, the possibility of inhibiting the replication and transcription processes and viral pathogenesis of SARS-COV-2 may be facilitated through the application of PG.

SUBMITTER: Samandar F

PROVIDER: S-EPMC9281425 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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1,2,3,4,6-Pentagalloyl glucose of Pistacia lentiscus can inhibit the replication and transcription processes and viral pathogenesis of SARS-COV-2.

Samandar Farzaneh F Amiri Tehranizadeh Zeinab Z Saberi Mohammad Reza MR Chamani Jamshidkhan J

Molecular and cellular probes 20220714

SARS-COV-2 stands as the source of the most catastrophic pandemic of this century, known as COVID-19. In this regard, we explored the effects of five Pistacia sp. active ingredients on the most crucial targets of SARS-COV-2, including 3CLpro, PLpro, RdRp, helicase, NSP15, and E protein. The results of molecular docking determined 1,2,3,4,6-pentagalloyl glucose (PG) as the most effective compound of Pistacia sp, which also confirmed its excellent binding affinities and stable interactions with he ...[more]

PMID: 35843391

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Project description:The outbreak of SARS-CoV-2 virus caused more than 80,155,187 confirmed COVID-19 cases worldwide, which has posed a serious threat to global public health and the economy. The development of vaccines and discovery of novel drugs for COVID-19 are urgently needed. Although the FDA-approved SARS-CoV-2 vaccines has been launched in many countries recently, the strength of safety, stringent storage condition and the possibly short-term immunized efficacy remain as the major challenges in the popularity and recognition of using vaccines against SARS-CoV-2. With the spike-receptor binding domain (RBD) of SARS-CoV-2 being responsible for binding to human angiotensin-converting enzyme 2 receptor (hACE2), ACE2 is identified as the receptor for the entry and viral infection of SARS-CoV-2. In this study, molecular docking and biolayer interferometry (BLI) binding assay were adopted to determine the direct molecular interactions between natural small-molecule, 1,2,3,4,6-Pentagalloyl glucose (PGG) and the spike-RBD of the SARS-CoV-2. Our results showed that PGG preferentially binds to a pocket that contains residues Glu 340 to Lys 356 of spike-RBD with a relatively low binding energy of -8 kcal/mol. BLI assay further confirmed that PGG exhibits a relatively strong binding affinity to SARS-CoV-2-RBD protein in comparison to hACE2. In addition, both ELISA and immunocytochemistry assay proved that PGG blocks SARS-CoV-2-RBD binding to hACE2 dose dependently in cellular level. Notably, PGG was confirmed to abolish the infectious property of RBD-pseudotyped lentivirus in hACE2 overexpressing HEK293 cells, which mimicked the entry of wild type SARS-CoV-2 virus in human host cells. Finally, maximal tolerated dose (MTD) studies revealed that up to 200 mg/kg/day of PGG was confirmed orally safe in mice. Our findings suggest that PGG may be a safe and potential antiviral agent against the COVID-19 by blockade the fusion of SARS-CoV-2 spike-RBD to hACE2 receptors. Therefore, PGG may be considered as a safe and natural antiviral agent for its possible preventive application in daily anti-virus hygienic products such as a disinfectant spray or face mask.

Project description:Hypertension poses a significant global health burden and is closely associated with cardiovascular morbidity. Pistacia lentiscus var. chia, commonly known as mastic, has emerged as a potential nutraceutical, due to its diverse pharmacological properties, including antioxidant and vasodilatory effects. Yet, its impact on hypertension in translational in vivo models and on hypertension-associated abnormalities in circulation, vasculature and kidneys have not been investigated. Herein we sought to decipher the putative antihypertensive potential of mastic, focusing on vascular and renal endothelium in clinically relevant in vivo models of essential hypertension. Two translational in vivo models of hypertension induced by Angiotensin II and Deoxycorticosterone acetate (DOCA)-High Salt in male rats, were utilized. Mastic administration at a therapeutic dose (220mg/kg, per os) was administered daily for four weeks, after the establishment of hypertension. Non-invasive blood pressure measurements and whole blood RNA sequencing and metabolomics were performed. Real-time PCR and Western blot analysis were conducted in kidney and aorta, to decipher its underlying antihypertensive mechanism. Mastic administration significantly reduced systolic, diastolic, and mean blood pressure in both in vivo hypertensive models. RNA sequencing revealed distinct gene expression profiles, with modulation of immune-related pathways in the Angiotensin II model and metabolic pathways in the DOCA-HS model. Additionally, RNA sequencing analysis revealed that mastic downregulated Rhob, Jun, Txnip and Egr1 mRNA expression in the circulation, paving towards a putative antioxidant and endothelial-targeted mechanism. Metabolomic analysis identified lysophosphatidylinositol upregulation as a consistent effect of mastic in both in vivo models, being implicated with improved endothelial homeostasis. RT-PCR analysis in the kidneys and aorta, showed that mastic increased endothelial markers such as Vegfa and Egr-1 mRNA expression in both experimental models. Concerning the endothelial homeostasis, mastic additionally increased renal nitric oxide synthase phosphorylation in both in vivo models of hypertension. This study highlights the potential of mastic as a natural adjuvant therapy for hypertension. The findings shed new light on its molecular mechanisms of action, providing insights into its protective impact on renal endothelium.

Project description:The rising risks of food microbial contamination and foodborne pathogens resistance have prompted an increasing interest in natural antimicrobials as promising alternatives to synthetic antimicrobials. Essential oils (EOs) obtained from natural sources have shown promising anticancer, antimicrobial, and antioxidant activities. EOs extracted from the resins of Pistacia lentiscus var. Chia are widely utilized for the treatment of skin inflammations, gastrointestinal disorders, respiratory infections, wound healing, and cancers. The therapeutic benefits of P. lentiscusessential oils (PO) are limited by their low solubility, poor bioavailability, and high volatility. Nanoencapsulation of PO can improve their physicochemical properties and consequently their therapeutic efficacy while overcoming their undesirable side effects. Hence, PO was extracted from the resins of P. lentiscusvia hydrodistillation. Then, PO was encapsulated into (2-hydroxypropyl)-beta-cyclodextrin (HPβCD) via freeze-drying. The obtained inclusion complexes (PO-ICs) appeared as round vesicles (22.62 to 63.19 nm) forming several agglomerations (180 to 350 nm), as detected by UHR-TEM, with remarkable entrapment efficiency (89.59 ± 1.47%) and a PDI of 0.1475 ± 0.0005. Furthermore, the encapsulation and stability of PO-ICs were confirmed via FE-SEM, 1H NMR, 2D HNMR (NOESY), FT-IR, UHR-TEM, and DSC. DSC revealed a higher thermal stability of the PO-ICs, reaching 351.0 °C. PO-ICs exerted substantial antibacterial activity against Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli as compared to free PO. PO-ICs showed significant enhancement in the antibacterial activity of the encapsulated PO against S. aureus with an MIC90 of 2.84 mg/mL and against P. aeruginosa with MIC90 of 3.62 mg/mL and MIC50 of 0.56 mg/mL. In addition, PO-ICs showed greater antimicrobial activity against E. coli by 6-fold with an MIC90 of 0.89 mg/mL, compared to free PO, which showed an MIC90 of 5.38 mg/mL. In conclusion, the encapsulation of PO into HPβCD enhanced its aqueous solubility, stability, and penetration ability, resulting in a significantly higher antibacterial activity.

Dataset Information

1,2,3,4,6-Pentagalloyl glucose of Pistacia lentiscus can inhibit the replication and transcription processes and viral pathogenesis of SARS-COV-2.

Publications

1,2,3,4,6-Pentagalloyl glucose of Pistacia lentiscus can inhibit the replication and transcription processes and viral pathogenesis of SARS-COV-2.

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