Flavonoid from Carica papaya inhibits NS2B-NS3 protease and prevents Dengue 2 viral assembly.
TL;DR: The flavonoid quercetin with highest binding energy against NS2B-NS3 protease which is evident by the formation of six hydrogen bonds with the amino acid residues at the binding site of the receptor is found.
Abstract: Dengue virus belongs to the virus family Flaviviridae. Dengue hemorrhagic disease caused by dengue virus is a public health problem worldwide. The viral non structural 2B and 3 (NS2B-NS3) protease complex is crucial for virus replication and hence, it is considered to be a good anti-viral target. Leaf extracts from Carica papaya is generally prescribed for patients with dengue fever, but there are no scientific evidences for its anti-dengue activity; hence we intended to investigate the anti-viral activity of compounds present in the leaves of Carica papaya against dengue 2 virus (DENV-2). We analysed the anti-dengue activities of the extracts from Carica papaya by using bioinformatics tools. Interestingly, we find the flavonoid quercetin with highest binding energy against NS2B-NS3 protease which is evident by the formation of six hydrogen bonds with the amino acid residues at the binding site of the receptor. Our results suggest that the flavonoids from Carica papaya have significant anti-dengue activities.
Abbreviations
ADME - Absorption, distribution, metabolism and excretion, BBB - Blood brain barrier, CYP - Cytochrome P450, DENV - – Dengue virus, DHF - Dengue hemorrhagic fever, DSS - Dengue shock syndrome, GCMS - – Gas chromatography- Mass spectrometry, MOLCAD - Molecular Computer Aided Design, NS - Non structural, PDB - Protein data bank, PMF - Potential Mean Force.
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TL;DR: In this article, the authors focused on the findings of current studies of the health-promoting aspects of Moringa and extract-related flavonoids on NCDs, particularly cancer, diabetes and obesity.
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TL;DR: The potential role of flavonoids in the modulation of signaling pathways that are crucial for COVID-19 disease, particularly those related to inflammation and immunity, was discussed in this paper.
91 citations
TL;DR: The aim of the present review is to summarize the data collected over the last five to six years on the mechanisms of the interactions of CYP with food constituents that occur via the direct binding of polyphenols to the enzymes and the mechanism of the regulation of CYp gene expression mediated by polyphenol.
Abstract: Cytochromes P450 (CYPs) are a large group of hemeproteins located on mitochondrial membranes or the endoplasmic reticulum They play a crucial role in the metabolism of endogenous and exogenous molecules The activity of CYP is associated with a number of factors including redox potential, protein conformation, the accessibility of the active site by substrates, and others This activity may be potentially modulated by a variety of small molecules Extensive experimental data collected over the past decade point at the active role of natural polyphenols in modulating the catalytic activity of CYP Polyphenols are widespread micronutrients present in human diets of plant origin and in medicinal herbs These compounds may alter the activity of CYP either via direct interactions with the enzymes or by affecting CYP gene expression The polyphenol–CYP interactions may significantly alter the pharmacokinetics of drugs and thus influence the effectiveness of chemical therapies used in the treatment of different
61 citations
TL;DR: Quercetin and fisetin down-regulate the production of proinflammatory cytokines induced by DENV infection enhanced by antibodies a mechanism involved in severe dengue.
Abstract: Background: There is a lack of specific antiviral therapy against dengue virus (DENV) in current use. Therefore, a great proportion of dengue cases progress to severe clinical forms due to a complex interplay between virus and host immune response. It has been hypothesized that heterotypic non-neutralizing antibodies enhance DENV infection in phagocytic cells, and this induces an inflammatory response that is involved in the pathogenesis of severe dengue. Purpose: To identify the antiviral and immunomodulatory effects of polyphenols on dengue virus infection. Methods: Human U937-DC-SIGN macrophages were infected with DENV serotypes 2 or 3 in the presence or not of enhancing antibody 4G2. Viral titers and the secretion of tumor necrosis factor-alpha, IL-6, IL-10 and interferon-alpha were analyzed timely. Results: DENV infection alone induced high production of IL-6 and TNF-α, but in the presence of 4G2 antibody, viral titers and TNF-α secretion were potentiated. Based on anti-inflammatory antecedents, the polyphenols curcumin, fisetin, resveratrol, apigenin, quercetin and rutin were tested for antiviral and immunomodulatory properties. Only quercetin and fisetin inhibited DENV-2 and DENV-3 infection in the absence or presence of enhancing antibody (>90%, p<0.001); they also inhibited TNF-α and IL-6 secretion (p<0.001). Conclusion: Quercetin and fisetin down-regulate the production of proinflammatory cytokines induced by DENV infection enhanced by antibodies a mechanism involved in severe dengue.
60 citations
TL;DR: Five out of nine phytochemicals are reported for the first time as novel DENV inhibitors.
Abstract: Background & objectives: Dengue fever, caused by dengue virus (DENV), has become a serious threat to human lives. Phytochemicals are known to have great potential to eradicate viral, bacterial and fungal-borne diseases in human beings. This study was aimed at in silico drug development against nonstructural protein 4B (NS4B) of dengue virus 4 (DENV4). Methods: A total of 2750 phytochemicals from different medicinal plants were selected for this study. These plants grow naturally in the climate of Pakistan and India and have been used for the treatment of various pathologies in human for long-time. The ADMET studies, molecular docking and density functional theory (DFT) based analysis were carried out to determine the potential inhibitory properties of these phytochemicals. Results: The ADMET analysis and docking results revealed nine phytochemicals, i.e. Silymarin, Flavobion, Derrisin, Isosilybin, Mundulinol, Silydianin, Isopomiferin, Narlumicine and Oxysanguinarine to have potential inhibitory properties against DENV and can be considered for additional in vitro and in vivo studies to assess their inhibitory effects against DENV replication. They exhibited binding affinity ≥−8 kcal/mol against DENV4-NS4B. Furthermore, DFT based analysis revealed high reactivity for these nine phytochemicals in the binding pocket of DENV4-NS4B, based on ELUMO, EHOMO and band energy gap. Interpretation & conclusion: Five out of nine phytochemicals are reported for the first time as novel DENV inhibitors. These included three phytochemicals from Silybum marianum, i.e. Derrisin, Mundulinol, Isopomiferin, and two phytochemicals from Fumaria indica, i.e. Narlumicine and Oxysanguinarine. However, all the nine phytochemicals can be considered for in vitro and in vivo analysis for the development of potential DENV inhibitors.
48 citations
References
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TL;DR: The goals of the PDB are described, the systems in place for data deposition and access, how to obtain further information and plans for the future development of the resource are described.
Abstract: The Protein Data Bank (PDB; http://www.rcsb.org/pdb/ ) is the single worldwide archive of structural data of biological macromolecules. This paper describes the goals of the PDB, the systems in place for data deposition and access, how to obtain further information, and near-term plans for the future development of the resource.
34,239 citations
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7,238 citations
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