Identification of therapeutic potential phytochemicals against the SARS CoV-2 spike protein of omicron variant by Molecular docking techniques DOI Open Access

Rathan Kumar

International Journal of Environment Agriculture and Biotechnology, Journal Year: 2022, Volume and Issue: 7(5), P. 196 - 217

Published: Jan. 1, 2022

Repeated mutations in the SARS CoV-2 have resulted emergence of various life-threatening variants including omicron, triggering a systemic crisis global human health. Due to unavailability any specific antiviral treatment, effectiveness currently available drugs or vaccines against this variant remains doubtful. Phytochemicals from their known medicinal plants were selected with antiviral, antifungal, anti-inflammatory, and antioxidant properties screened study therapeutic potential druglikeliness properties. A library 15 phytochemicals was constructed binding energies calculated by docking them spike protein omicron using AutoDock software. Subsequently, pharmacokinetic like ADME drug likeliness also calculated. Hydroxychloroquine (HCQ), an antimalarial chosen as standard analysis, displaying energy -5.22 kcal/mol whereas, Glycyrrhetic acid showed highest value -9.02 kcal/mol. Besides, all these higher (≤ -7.00 kcal/mol) better leading viable candidate treat infection caused variant.

Language: Английский

Glucose Epimerization‐Modulated Phytochemicals Constructing Carrier‐Free Hydrogel for Regulation of Macrophage Phenotype to Promote Wound Healing DOI

Jihui Lu,

Haoqiang Zhao, Zhijia Wang

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(22)

Published: Feb. 8, 2024

Abstract The self‐assembly of phytochemicals with multiple chiral centers is receiving significant attention for its potential in biomedical applications. However, the impact single center epimerization on molecular remains unexplored. Herein, behavior and bioactivities 1,2,3,4,6‐penta‐O‐galloyl‐α‐D‐glucose (α‐D‐PGG) 1,2,3,4,6‐penta‐O‐galloyl‐β‐D‐glucose (β‐D‐PGG) examined, a pair natural ellagitannins abundant plants. Interestingly, β‐D‐PGG formed hydrogel without modification, while α‐D‐PGG does not. This occurred due to balanced distribution aromatic rings phenolic hydroxyl groups β‐D‐PGG, facilitating via hydrogen bonding π – stacking into nanofibers. In contrast, α‐D‐PGG's inhibited by steric hindrance. Notably, demonstrated exceptional antibacterial activity regulating macrophage polarization toward M2 phenotype, thereby reducing inflammation. study not only reveals distinct behaviors glucose derivatives but also offers new insights their applications, such as wound healing.

Language: Английский

Citations

16

18β-Glycyrrhetinic acid protects against deoxynivalenol-induced liver injury via modulating ferritinophagy and mitochondrial quality control DOI
Junze Jiang,

Xintong Zhou,

Hao Chen

et al.

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 471, P. 134319 - 134319

Published: April 21, 2024

Language: Английский

Citations

11

Discovering common pathogenetic processes between COVID-19 and sepsis by bioinformatics and system biology approach DOI Creative Commons
Lu Lu, Leping Liu, Rong Gui

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 31, 2022

Corona Virus Disease 2019 (COVID-19), an acute respiratory infectious disease caused by severe syndrome coronavirus-2 (SARS-CoV-2), has spread rapidly worldwide, resulting in a pandemic with high mortality rate. In clinical practice, we have noted that many critically ill or patients COVID-19 present typical sepsis-related manifestations, including multiple organ dysfunction syndrome, coagulopathy, and septic shock. addition, it been demonstrated some pathological similarities sepsis, such as cytokine storm, hypercoagulable state after blood balance is disrupted neutrophil dysfunction. Considering the parallels between non-SARS-CoV-2 induced sepsis (hereafter referred to sepsis), aim of this study was analyze underlying molecular mechanisms these two diseases bioinformatics systems biology approach, providing new insights into pathogenesis development treatments. Specifically, gene expression profiles were obtained from Gene Expression Omnibus (GEO) database compared extract common differentially expressed genes (DEGs). Subsequently, DEGs used investigate genetic links sepsis. Based on enrichment analysis DEGs, pathways closely related inflammatory response observed, Cytokine-cytokine receptor interaction pathway NF-kappa B signaling pathway. protein-protein networks regulatory constructed, results showed ITGAM may be potential key biomarker base analysis. Furthermore, diagnostic model risk prediction nomogram for constructed using machine learning methods. Finally, therapeutic agents, progesterone emetine, screened through drug-protein docking simulations. We hope provide strategies future research treatment elucidating

Language: Английский

Citations

36

The role of peroxisome proliferator-activated receptors in the modulation of hyperinflammation induced by SARS-CoV-2 infection: A perspective for COVID-19 therapy DOI Creative Commons
Aliakbar Hasankhani, Abolfazl Bahrami, Bahareh Tavakoli‐Far

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 17, 2023

Coronavirus disease 2019 (COVID-19) is a severe respiratory caused by infection with acute syndrome coronavirus 2 (SARS-CoV-2) that affects the lower and upper tract in humans. SARS-CoV-2 associated induction of cascade uncontrolled inflammatory responses host, ultimately leading to hyperinflammation or cytokine storm. Indeed, storm hallmark immunopathogenesis, directly related severity mortality COVID-19 patients. Considering lack any definitive treatment for COVID-19, targeting key factors regulate response patients could be fundamental step developing effective therapeutic strategies against infection. Currently, addition well-defined metabolic actions, especially lipid metabolism glucose utilization, there growing evidence central role ligand-dependent nuclear receptors peroxisome proliferator-activated (PPARs) including PPARα, PPARβ/δ, PPARγ control signals various human diseases. This makes them attractive targets approaches control/suppress hyperinflammatory COVID-19. In this review, we (1) investigate anti-inflammatory mechanisms mediated PPARs their ligands during infection, (2) on basis recent literature, highlight importance PPAR subtypes development promising

Language: Английский

Citations

14

In vitro simulated gastrointestinal digestion stability and in vivo antihypertensive effect of the peptide KYPHVF and its network pharmacology DOI Creative Commons

Renjuan Li,

Yongliang Zhuang,

Lin Lin

et al.

Journal of Functional Foods, Journal Year: 2023, Volume and Issue: 107, P. 105672 - 105672

Published: July 5, 2023

Previous study showed KYPHVF has a high angiotensin-converting enzyme (ACE) inhibitory activity. This aimed to further explore the in vitro simulated gastrointestinal digestion stability, vivo antihypertensive, and network pharmacology of KYPHVF. Results that was stable during vitro. absorbed intact form by Caco-2 cell monolayer with transport percentage 2.00%, partially hydrolyzed produce YPHVF PHVF through monolayer. The blood pressures Spontaneous hypertensive rats (SHRs) decreased after oral administration KYPHVF, might antihypertensive effect lowering ACE contents serum kidney SHRs. Furthermore, results indicated had 44 potential targets, showing multi-target multi-pathway characteristics. Molecular docking strong binding force affinity key targets.

Language: Английский

Citations

14

Unveiling the mechanism of amelioration of adjuvant-induced rheumatoid arthritis by Drynaria quercifolia rhizome extract using network pharmacology and gene expression-based studies DOI Creative Commons
Debabrata Modak, Subhajit Ghosh, Sourav Sarkar

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 8, 2025

Rhizomes of Drynaria quercifolia have long been traditionally used to manage rheumatic pain. However, there is limited research supporting this traditional practice and insufficient evidence demonstrating the molecular mechanisms action plant-derived bioactives in rheumatoid arthritis (RA). The current study aims identify effective components methanol rhizome extract (DME) their probable pharmacological alleviating Rheumatoid Arthritis (RA) using network-pharmacology, docking, molecular-dynamics simulations, gene expression-based validation. Gas chromatography-mass spectrometry (GC-MS) based screening identified 41 volatile phytocomponents from DME having drug-like potentiality. Network pharmacology-based revealed 117 therapeutic targets for RA which 11 as core targets. Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) enrichment analysis indicated that key target genes were mostly enriched inflammatory response associated with multiple signalling pathways. Molecular docking dynamics studies proteins like serine/threonine-protein kinase (AKT1), peroxisome proliferator-activated receptor alpha (PPARA), gamma (PPARG), exhibited strong binding affinity stable interactions present DME. For experimental verification FCA (Freund's complete adjuvant)-induced chronic model employed further investigation. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) results validated significantly (p ≤ 0.05) regulate expression AKT PPARG model. Moreover, confirmed downregulated pro-inflammatory mediators COX-2, IL-6 TNF-α at protein levels also normalized different oxidative stress parameters both low high dose groups DME-treated arthritic animals. In conclusion, network-based silico approach probably act a synergistic way modulate RA, was by studies. Therefore, could be potential alternative immunomodulatory therapies combat related conditions.

Language: Английский

Citations

0

Structure–Activity relationship (SAR) of 18β-glycyrrhetinic acid derivatives on their antitumor activity through the PPARγ receptor and caspase-3 pathway DOI Creative Commons
Juan Sun,

Qi Zheng,

Yiheng Zhang

et al.

Journal of Saudi Chemical Society, Journal Year: 2024, Volume and Issue: 28(2), P. 101815 - 101815

Published: Jan. 15, 2024

Licorice is extensively utilized in the food industry, and glycyrrhetinic acid among most critical active constituents licorice. This ingredient has garnered increasing attention recent years. In a previous study, we identified new series of Glycyrrhetinic derivatives containing piperazine skeleton, using virtual screening techniques based on docking. this conducted further optimization lead compound 4c, with focus enhancing hydrophobic interactions binding site to improve agonist efficacy for peroxisome proliferator-activated receptor γ (PPARγ). The obtained compounds were characterized 1H NMR, 13C HRMS, HPLC. Furthermore, these evaluated strong antitumor activity. Some potent activities tested their PPARγ Especially, 4f showed activity half maximal inhibitory concentration (IC50) values 2.382 μM against tumor cell lines Siha. Docking simulation was performed position into determine probable conformation. Consequently, discovered novel that demonstrated high vitro

Language: Английский

Citations

3

In silico and in vitro studies of Taiwan Chingguan Yihau (NRICM101) on TNF-α/IL-1β-induced Human Lung Cells DOI Creative Commons
Yih‐Dih Cheng, Chi‐Cheng Lu, Yuan‐Man Hsu

et al.

Biomedicine, Journal Year: 2022, Volume and Issue: 12(3), P. 56 - 71

Published: Aug. 28, 2022

COVID-19 pandemic has been a global outbreak of coronavirus (SARS-CoV-2 virus) since 2019. Taiwan Chingguan Yihau (NRICM101) is the first traditional Chinese medicine (TCM) classic herbal formula and widely used for patients in more than 50 nations. This study to investigate silico target fishing components NRICM101 explore whether inhibits cytokines-induced normal human lung cell injury vitro. Our results showed that network prediction by high throughput screening platform multiple functions may affect cytokine regulation prevent injury. In addition, revealed protective effects against TNF-α/IL-1β-induced HEL 299 through JNK p38MAPK kinase signaling. Next-generation sequencing (NGS) analysis on TNF-α/IL-1β-injured cells indicated inflammatory pathway, movement macrophages, cellular infiltration Th1/Th2 immuno-regulation pathways were included. Thus, therapeutic agent, it can improve syndrome confer beneficial targeting mechanisms.

Language: Английский

Citations

14

Drug Repurposing Using Gene Co-Expression and Module Preservation Analysis in Acute Respiratory Distress Syndrome (ARDS), Systemic Inflammatory Response Syndrome (SIRS), Sepsis, and COVID-19 DOI Creative Commons
Ryan Christian Mailem, Lemmuel L. Tayo

Biology, Journal Year: 2022, Volume and Issue: 11(12), P. 1827 - 1827

Published: Dec. 15, 2022

SARS-CoV-2 infections are highly correlated with the overexpression of pro-inflammatory cytokines in what is known as a cytokine storm, leading to high fatality rates. Such accompanied by SIRS, ARDS, and sepsis, suggesting potential link between three phenotypes. Currently, little about transcriptional similarity these conditions. Herein, weighted gene co-expression network analysis (WGCNA) clustering was applied RNA-seq datasets (GSE147902, GSE66890, GSE74224, GSE177477) identify modules co-expressed genes, cross referenced dataset GSE160163, across samples. To assess transcriptome similarities conditions, module preservation performed functional enrichment analyzed DAVID webserver. The hub genes significantly preserved were identified, classified into upregulated or downregulated, used screen candidate drugs using Connectivity Map (CMap) repurposed drugs. Results show that several immune pathways (chemokine signaling, NOD-like Th1 Th2 cell differentiation) conserved four diseases. Hub screened intramodular connectivity significant relevance pathogenesis storms. Transcriptomic-driven drug repurposing identified seven (SB-202190, eicosatetraenoic-acid, loratadine, TPCA-1, pinocembrin, mepacrine, CAY-10470) targeted immune-related processes. These warrant further study their efficacy for treating storms, vitro vivo experiments recommended confirm findings this study.

Language: Английский

Citations

14

Glycyrrhizin and boswellic acids, the golden nutraceuticals: multitargeting for treatment of mild–moderate COVID-19 and prevention of post-COVID cognitive impairment DOI Creative Commons
Adel A. Gomaa,

Yasmin A. Abdel-Wadood,

Mohamed Gomaa

et al.

Inflammopharmacology, Journal Year: 2022, Volume and Issue: 30(6), P. 1977 - 1992

Published: Sept. 22, 2022

Abstract Breakthrough infections have been reported in fully vaccinated persons. Furthermore, rebound symptoms following the new FDA granted emergency use to combat SARS-CoV-2. Glycyrrhizin (GR) and boswellic acids (BAs) combination has shown highly successful actions against COVID-19 our recent clinical trial. However, study is limited by small sample size, therefore, aim of this article comprehensively evaluate evidence on efficacy GR BAs preventing development patients with mild moderate post-COVID-19 cognitive impairment, which most important symptom after recovery from Covid-19 disease. We reviewed discussed information published since outbreak pandemic until July 2022 preclinical (in vivo, vivo bioinformatics) studies related antiviral, anti-inflammatory immunomodulatory activity Gr BAs. Sixteen were performed determine Ten used primarily for vitro assays six molecular docking studies. antiviral SARS-CoV-2 was determined only five using modeling bioinformatics. All these confirmed that n strong can be as a therapeutic agent protective They may act inhibiting main protease (Mpro) responsible replication blocking spike protein-mediated cell entry. Only seven rigorously designed trials regarding usefulness GR, or their combinations treatment 2022. Although there no impairment so far, several demonstrated potential effect prevention molecules activate inflammatory signaling pathway. In conclusion, findings documented beneficial treat its variants prevent post-COVID impairment. it warrants further larger randomized size ensure sufficient benefits symptoms.

Language: Английский

Citations

8