Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols

Food Chemistry, Год журнала: 2021, Номер 373, С. 131594 - 131594

Опубликована: Ноя. 14, 2021

The abundance of polyphenols in edible plants makes them an important component human nutrition. Considering the ongoing COVID-19 pandemic, a number studies have investigated as bioactive constituents. We applied in-silico molecular docking well dynamics supported by in-vitro assays to determine inhibitory potential various plant against SARS-CoV-2 therapeutic target, protease 3CLpro. Of initial screening, quercetin, ellagic acid, curcumin, epigallocatechin gallate and resveratrol showed IC50 values 11.8 µM 23.4 µM. In-silico simulations indicated stable interactions with 3CLpro active site over 100 ns production runs. Moreover, surface plasmon resonance spectroscopy was used measure binding real time. Therefore, we provide evidence for inhibition natural polyphenols, suggest further research into development these novel inhibitors or biochemical probes.

Язык: Английский

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Resveratrol and Pterostilbene Inhibit SARS-CoV-2 Replication in Air–Liquid Interface Cultured Human Primary Bronchial Epithelial Cells

Viruses, Год журнала: 2021, Номер 13(7), С. 1335 - 1335

Опубликована: Июль 10, 2021

The current COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has an enormous impact on human health economy. In search for therapeutic options, researchers have proposed resveratrol, a food supplement with known antiviral, anti-inflammatory, antioxidant properties as advantageous antiviral therapy SARS-CoV-2 infection. Here, we provide evidence that both resveratrol its metabolically more stable structural analog, pterostilbene, exhibit potent against in vitro. First, show pterostilbene activity African green monkey kidney cells. Both compounds actively inhibit virus replication within infected cells reduced progeny production was observed when the compound added at post-inoculation conditions. Without replenishment of compound, up to roughly five rounds replication, demonstrating long-lasting effect these compounds. Second, upper tract represents initial site also assessed air–liquid interface (ALI) cultured primary bronchial epithelial cells, isolated from healthy volunteers. Resveratrol showed strong 48 h post-infection. Collectively, our data indicate are promising Because results represent laboratory findings advocate evaluation clinical trials before statements made whether drugs treatment.

Язык: Английский

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Influenza Virus Down-Modulates G6PD Expression and Activity to Induce Oxidative Stress and Promote Its Replication

Frontiers in Cellular and Infection Microbiology, Год журнала: 2022, Номер 11

Опубликована: Янв. 6, 2022

Influenza virus infection induces oxidative stress in host cells by decreasing the intracellular content of glutathione (GSH) and increasing reactive oxygen species (ROS) level. Glucose-6-phosphate dehydrogenase (G6PD) is responsible for production reducing equivalents nicotinamide adenine dinucleotide phosphate (NADPH) that used to regenerate reduced form GSH, thus restoring redox homeostasis. Cells deficient G6PD display elevated levels ROS an increased susceptibility viral infection, although consequences modulation during remain be elucidated. In this study, we demonstrated influenza decreases expression activity, resulting increase replication. Moreover, down regulation correlated with a decrease nuclear factor erythroid 2-related 2 (NRF2), key transcription regulates antioxidant response gene network. Also down-regulated infected was sirtuin (SIRT2), NADPH-dependent deacetylase involved activity. Acetylation manner strictly dependent on SIRT2 expression. Furthermore, use pharmacological activator rescued GSH NRF2 expression, leading decreased Overall, these data identify novel strategy induce favor its replication cells. These observations furthermore suggest manipulation metabolic pathways could define new therapeutic strategies interfere infection.

Язык: Английский

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Direct regulation of shikimate, early phenylpropanoid, and stilbenoid pathways by Subgroup 2 R2R3‐MYBs in grapevine

The Plant Journal, Год журнала: 2022, Номер 110(2), С. 529 - 547

Опубликована: Янв. 29, 2022

The stilbenoid pathway is responsible for the production of resveratrol in grapevine (Vitis vinifera L.). A few transcription factors (TFs) have been identified as regulators this but extent control has not deeply studied. Here we show how DNA affinity purification sequencing (DAP-Seq) allows genome-wide TF-binding site interrogation grape. We obtained 5190 and 4443 binding events assigned to 4041 3626 genes MYB14 MYB15, respectively (approximately 40% peaks located within −10 kb start sites). DAP-Seq MYB14/MYB15 was combined with aggregate gene co-expression networks (GCNs) built from more than 1400 transcriptomic datasets leaves, fruits, flowers narrow down bound a set high confidence targets. analysis MYB14, MYB13, third uncharacterized member Subgroup 2 (S2), showed that addition previously known stilbene synthase (STS) targets, these bind 30 47 STS family genes. Moreover, all three MYBs several PAL, C4H, 4CL genes, shikimate WRKY03 co-regulator resveratrol-modifying candidates among which ROMT2-3 were validated enzymatically. proportion induced activated transcriptomes transient MYB15-overexpressing validating our methodological approach delimiting TF Overall, R2R3-MYBs appear play key role directly regulating primary secondary metabolic steps leading an increased flux towards production. integration reciprocal GCNs offers rapid framework function characterization using approaches context non-model plant species stands up valid first identifying regulatory specialized metabolism.

Язык: Английский

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‘Poly phenolic phytoceutical loaded nano-bilosomes for enhanced caco-2 cell permeability and SARS-CoV 2 antiviral activity’: in-vitro and insilico studies

Drug Delivery, Год журнала: 2023, Номер 30(1)

Опубликована: Янв. 1, 2023

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) predisposed to the emergence of worldwide catastrophe that impels evolution safe and effective therapeutic system. Polyphenols as resveratrol (RSV) exhibit a well evidenced antiviral activity. Unfortunately, like most phenolic nutraceuticals, RSV suffers from restrained solubility massive degradation in GIT liver which turn prohibit its clinical use. Herein, PEGylated bilosomes (PBs) contain edge activator along with traditional components (Span 60, cholesterol bile salts) were proposed boost both permeability bioavailability RSV. The investigation prominent effect diverse variables on characteristics vesicles picking optimum formula conducted via construction 23 factorial experiment. appraisal formulae was basis entrapment efficiency percent (EE%), particle size (PS) zeta potential (ZP). In addition, spherical shaped optimal (F5) exhibited EE% 86.1 ± 2.9%, PS 228.9 8.5 nm, ZP -39.8 1.3 mV. sorted superior dissolution behaviors, boosted Caco-2 cells cellular uptake by round 4.7 folds relative dispersion. F5 demonstrated complete vitro suppression SARS-CoV-2 at concentration 0.48 μg/ml 6.6 times enhancement activity accomplished molecular modeling heavily provided proof for possible interactions key residues SARS-CoV2 Mpro enzyme. Finally, could be promising oral panel curation infection.

Язык: Английский

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Effectiveness of Drug Repurposing and Natural Products Against SARS-CoV-2: A Comprehensive Review

Clinical Pharmacology Advances and Applications, Год журнала: 2024, Номер Volume 16, С. 1 - 25

Опубликована: Янв. 1, 2024

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a betacoronavirus responsible for the COVID-19 pandemic, causing respiratory disorders, and even death in some individuals, if not appropriately treated time. To face preventive measures have been taken against contagions application of vaccines to prevent severe disease cases. For treatment, antiviral, antiparasitic, anticoagulant other drugs reused due limited specific medicaments disease. Drug repurposing an emerging strategy with therapies that already tested safe humans. One promising alternative systematic experimental screening vast pool compounds computational drug (in silico assay). Using these tools, new uses approved such as chloroquine, hydroxychloroquine, ivermectin, zidovudine, ribavirin, lamivudine, remdesivir, lopinavir tenofovir/emtricitabine conducted, showing effectiveness vitro SARS-CoV-2 these, also clinical trials. Additionally, therapeutic options sought natural products (terpenoids, alkaloids, saponins phenolics) results use Among most studied are resveratrol, quercetin, hesperidin, curcumin, myricetin betulinic acid, which were proposed inhibitors. control SARS-CoV2, better observed remdesivir hospitalized patients outpatients. Regarding products, quercetin demonstrated antiviral activity vivo, nebulized formulation has alleviate symptoms COVID-19. This review shows evidence efficacy potential treatment this, search was carried out PubMed, SciELO ScienceDirect databases articles about or under study recognized their SARS-CoV-2.

Язык: Английский

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Neurovascular coupling impairment as a mechanism for cognitive deficits in COVID-19

Brain Communications, Год журнала: 2024, Номер 6(2)

Опубликована: Янв. 1, 2024

Abstract Components that comprise our brain parenchymal and cerebrovascular structures provide a homeostatic environment for proper neuronal function to ensure normal cognition. Cerebral insults (e.g. ischaemia, microbleeds infection) alter cellular physiologic processes within the neurovascular unit contribute cognitive dysfunction. COVID-19 has posed significant complications during acute convalescent stages in multiple organ systems, including brain. Cognitive impairment is prevalent complication patients, irrespective of severity SARS-CoV-2 infection. Moreover, overwhelming evidence from vitro, preclinical clinical studies reported SARS-CoV-2-induced pathologies components are associated with impairment. Neurovascular disruption alters coupling response, critical mechanism regulates cerebromicrovascular blood flow meet energetic demands locally active neurons. Normal processing achieved through response involves coordinated action cells (i.e. neurons glia) cell types endothelia, smooth muscle pericytes). However, current work on COVID-19-induced yet investigate as causal factor. Hence, this review, we aim describe SARS-CoV-2's effects how they can impact decline disease. Additionally, explore potential therapeutic interventions mitigate Given great both individuals public health, necessity effort fundamental scientific research application becomes imperative. This integrated endeavour crucial mitigating deficits induced by its subsequent burden especially vulnerable population.

Язык: Английский

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Antioxidant-Rich Functional Foods and Exercise: Unlocking Metabolic Health Through Nrf2 and Related Pathways

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 1098 - 1098

Опубликована: Янв. 27, 2025

This article reviews the synergistic effects of antioxidant-enriched functional foods and exercise in improving metabolic health, focusing on underlying molecular mechanisms. The review incorporates evidence from PubMed, SCOPUS, Web Science, PsycINFO, reference lists relevant up to 20 December 2024, highlighting central role Nrf2 pathway. As a critical regulator oxidative stress adaptation, mediates benefits these interventions. presents an innovative approach understanding regulation inflammation, its potential prevention treatment various diseases, including cancer, neurodegenerative disorders, cardiovascular pulmonary diabetes, inflammatory conditions, ageing, infections such as COVID-19. novelty this study is investigate bioactive compounds found (such polyphenols, flavonoids, vitamins) exercise-induced activation combined reveals their improve insulin sensitivity lipid metabolism reduce offering promising strategy for management chronic diseases. However, there are significant gaps current research, particularly regarding mechanisms interaction between diet, physical activity, activation, well long-term different populations, those with In addition, interactions other signalling pathways, AMPK, NF-κB, PI3K/Akt, collective contributions health explored. Furthermore, novel biomarkers presented assess impact strategies, NAD+/NADH ratio, GSH markers mitochondrial health. findings provide valuable insights into how integration antioxidant-rich diet regular can by activating related pathways represent strategies disorders. Further studies needed fully understand therapeutic interventions diseases stress, disease, cancer.

Язык: Английский

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The Natural Stilbenoid (–)-Hopeaphenol Inhibits Cellular Entry of SARS-CoV-2 USA-WA1/2020, B.1.1.7, and B.1.351 Variants

Antimicrobial Agents and Chemotherapy, Год журнала: 2021, Номер 65(12)

Опубликована: Сен. 20, 2021

Antivirals are urgently needed to combat the global SARS-CoV-2/COVID-19 pandemic, supplement existing vaccine efforts, and target emerging SARS-CoV-2 variants of concern. Small molecules that interfere with binding viral spike receptor domain (RBD) host angiotensin-converting enzyme II (ACE2) may be effective inhibitors cell entry. Here, we screened 512 pure compounds derived from natural products using a high-throughput RBD/ACE2 assay identified (-)-hopeaphenol, resveratrol tetramer, in addition vatalbinoside A vaticanol B, as potent selective For example, (-)-hopeaphenol disrupted 50% inhibitory concentration (IC50) 0.11 μM, contrast an IC50 28.3 μM against unrelated ligand/receptor pair PD-1/PD-L1 (selectivity index, 257.3). When assessed USA-WA1/2020 variant, also inhibited entry VSVΔG-GFP reporter pseudovirus expressing into ACE2-expressing Vero-E6 cells vitro replication infectious virus cytopathic effect yield reduction assays (50% concentrations [EC50s], 10.2 23.4 μM) without cytotoxicity approaching activities control antiviral remdesivir (EC50s, 1.0 7.3 μM). Notably, two concern, B.1.1.7/Alpha B.1.351/Beta both spike-containing similar or improved over variant. These results identify related stilbenoid analogues across multiple

Язык: Английский

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The potential role of resveratrol as supportive antiviral in treating conditions such as COVID-19 – A formulator’s perspective

Biomedicine & Pharmacotherapy, Год журнала: 2022, Номер 148, С. 112767 - 112767

Опубликована: Фев. 28, 2022

With an increased transmissibility but milder form of disease the omicron variant COVID-19 and newer antivirals often still out reach many populations, a refocus current treatment regimens is required. Safe, affordable, available adjuvant treatments should also be considered known drugs substances need to repurposed tested. Resveratrol, well-known antioxidant natural origin, shown act as antiviral well playing role in immune stimulation, down regulation pro-inflammatory cytokine release reducing lung injury by oxidative stress, such option. New initiatives collaborations will however found unleash resveratrol's full potential pharmaceutical market.

Язык: Английский

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