scholarly journals Triphala in Traditional Ayurvedic Medicine Inhibits Dengue Virus Infection in Huh7 Hepatoma Cells

2021 ◽  
Vol 14 (12) ◽  
pp. 1236
Author(s):  
Aussara Panya ◽  
Kanyaluck Jantakee ◽  
Suthida Punwong ◽  
Supawadee Thongyim ◽  
Thida Kaewkod ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Gallic Acid ◽  
Biological Activities ◽  
Virus Production ◽  
Vero Cells ◽  
Denv Infection ◽  
High Ratio ◽  
Infection Treatment ◽  
Huh7 Cells ◽  
Antiviral Mechanism

Traditional Triphala (three fruits), consisting of Phyllanthus emblica, Terminalia chebula, and Terminalia bellirica, presents a broad range of biological activities. However, its ability to inhibit dengue virus (DENV) infection has not been reported yet. Herein, the authors investigated the efficiency of three different Triphala formulations and its individual extract constituents to inhibit DENV infection. Treatment with T. bellirica extract or Triphala formulated with a high ratio of T. bellirica extract showed remarkable efficiency in significantly lowering DENV infection in Vero cells. Their effects were further studied in Huh7 cells, to address its potential ability in human cells. Treatment with 100 μg/mL of T. bellirica extract or Triphala resulted in an approximate 3000-fold or 1000-fold lowering of virus production, respectively. Furthermore, the treatment diminished IL-6 and CXCL-10 expressions, which are the hallmark of the cytokine storm phenomenon in DENV infection. The HPLC profiling demonstrated gallic acid as a major compound, the treatment by which showed its ability to effectively inhibit DENV infection after virus entry. Molecular docking demonstrated that gallic acid was able to interact with DENV NS5 protein, which could be one of Triphala’s antiviral mechanism. This study offers Triphala formulation and its ingredient, T. bellirica extract, as a natural based pharmaceutical to be used in DENV infection treatment.

scholarly journals Chemical Composition, Antifungal, and Cytotoxicity Activities of Inga laurina (Sw.) Willd Leaves

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Carla de Moura Martins ◽  
Sérgio A. L. de Morais ◽  
Mário M. Martins ◽  
Luís C. S. Cunha ◽  
Cláudio V. da Silva ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Gallic Acid ◽  
Total Phenolics ◽  
Biological Activities ◽  
Ethanolic Extract ◽  
Ethyl Acetate Fraction ◽  
Vero Cells ◽  
Quercetin Glycosides ◽  
Cytotoxicity Activities ◽  
First Time

The species Inga laurina is native to the Brazilian Cerrado. There are no studies about the chemical composition and biological activities of extracts of this endangered species. The ethanolic extract and its successive fractions are rich in phenolic compounds and presented good antifungal activities. HPLC/MS-MS/MS and H1/C13 analysis led to the identification of seventeen compounds, most of which are gallic acid derivatives, myricetin and quercetin glycosides. The ethyl acetate fraction (EAF) contained high levels of total phenolics, expressed in milligrams of gallic acid equivalents per gram of extract (475.3 ± 1.9 mg GAE gextract-1) and flavonoids expressed in milligrams of quercetin equivalents per gram of extract (359.3 ± 10.6 mg QE gextract-1). This fraction was active against fungi of the Candida genus. The EAF showed MIC value 11.7 μg mL−1 against C. glabrata and a selectivity index of 1.6 against Vero cells. The flavonol glycoside myricetin-3-O-rhamnoside was isolated for the first time from the Inga laurina. These results make I. laurina a promising plant as a source of pharmaceutical and biological active antifungal compounds.

scholarly journals A Synthetic Bioactive Peptide Derived from the Asian Medicinal Plant Acacia catechu Binds to Dengue Virus and Inhibits Cell Entry

Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1267
Author(s):  
Aussara Panya ◽  
Nunghathai Sawasdee ◽  
Pucharee Songprakhon ◽  
Yingmanee Tragoolpua ◽  
Siriphorn Rotarayanont ◽  
...  
Keyword(s):  
Medicinal Plant ◽  
Dengue Virus ◽  
Chemical Properties ◽  
Virus Production ◽  
Denv Infection ◽  
Bioactive Peptide ◽  
Effective Vaccine ◽  
Attractive Alternative ◽  
Denv Serotypes ◽  
Acacia Catechu

Dengue virus (DENV) infection has become a critically important globally prevalent infectious disease, especially in tropical and subtropical countries. Since neither currently exists, there is an urgent need for an effective vaccine to prevent, and a specific drug to treat DENV infection. Therapeutic peptides represent an attractive alternative for development into anti-DENV drugs due to their safety and their diverse biological and chemical properties. We recently reported novel bioactive peptides extracted from the Asian medicinal plant Acacia catechu that efficiently inhibited all four DENV serotypes. In this study, we investigated the anti-DENV activity of a synthetic bioactive peptide derived from this plant. The most effective peptide (designated Pep-RTYM) inhibited DENV infection with a half-maximal inhibition concentration value of 7.9 μM. Time-of-addition study demonstrated that Pep-RTYM interacted with DENV particles and inhibited cellular entry. Pep-RTYM at 50 μM significantly reduced DENV production in Vero-kidney epithelial cells about 1000-fold, but it could decrease the virus production in Huh7 hepatocyte cells approximately 40-fold. Binding of Pep-RTYM to DENV particles may prevent virus interaction with cellular receptor and subsequent virus entry. This finding suggests a potential role of Pep-RTYM in the development of a novel anti-DENV drug.

scholarly journals Crocetin Improves Dengue Virus-Induced Liver Injury

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 825
Author(s):  
Gopinathan Pillai Sreekanth ◽  
Aporn Chuncharunee ◽  
Pa-thai Yenchitsomanus ◽  
Thawornchai Limjindaporn
Keyword(s):  
Polymerase Chain Reaction ◽  
Liver Injury ◽  
Dengue Virus ◽  
Real Time ◽  
Nuclear Translocation ◽  
Virus Production ◽  
Denv Infection ◽  
Chain Reaction ◽  
Gene Expressions ◽  
Polymerase Chain

Dengue virus (DENV) infection is one of the most widespread mosquito-borne viral infections. Liver injury is commonly observed in severe DENV infection, and the present study aimed to examine the efficacy of crocetin treatment in an immunocompetent mouse model of DENV infection exhibiting liver injury. The efficacy of crocetin treatment in DENV-induced liver injury was assessed via both transaminase levels and histopathology analysis. A real-time polymerase chain reaction array was then used to describe the expression of 84 apoptosis-related genes. Using real-time RT-PCR and Western blot analysis, the gene expressions of host factors were investigated. Additionally, the effect of crocetin in NF-kB signaling during DENV infection was studied. We did not observe any significant reduction in virus production when DENV-infected mice were treated with crocetin. However, DENV-infected mice treated with crocetin showed reduced DENV-induced apoptosis. The real-time polymerase chain reaction array revealed pro-inflammatory cytokine expressions to be significantly reduced in the crocetin-treated DENV-infected mice. We also found that crocetin could effectively modulate antioxidant status in DENV-infected mice. Moreover, crocetin demonstrated the ability to reduce the nuclear translocation of NF-kB in DENV-infected mice. Our results suggest that crocetin treatment does not inhibit DENV replication in the liver of DENV-infected mice; however, we did find that crocetin improves host responses that reduce liver injury.

scholarly journals Delivery of antiviral small interfering RNA with gold nanoparticles inhibits dengue virus infection in vitro

2014 ◽  
Vol 95 (8) ◽  
pp. 1712-1722 ◽  
Author(s):  
Amber M. Paul ◽  
Yongliang Shi ◽  
Dhiraj Acharya ◽  
Jessica R. Douglas ◽  
Amanda Cooley ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Dengue Virus ◽  
Sirna Delivery ◽  
Vero Cells ◽  
Denv Infection ◽  
Small Interfering Rnas ◽  
Virion Release ◽  
Life Threatening

Dengue virus (DENV) infection in humans can cause flu-like illness, life-threatening haemorrhagic fever or even death. There is no specific anti-DENV therapeutic or approved vaccine currently available, partially due to the possibility of antibody-dependent enhancement reaction. Small interfering RNAs (siRNAs) that target specific viral genes are considered a promising therapeutic alternative against DENV infection. However, in vivo, siRNAs are vulnerable to degradation by serum nucleases and rapid renal excretion due to their small size and anionic character. To enhance siRNA delivery and stability, we complexed anti-DENV siRNAs with biocompatible gold nanoparticles (AuNPs) and tested them in vitro. We found that cationic AuNP–siRNA complexes could enter Vero cells and significantly reduce DENV serotype 2 (DENV-2) replication and infectious virion release under both pre- and post-infection conditions. In addition, RNase-treated AuNP–siRNA complexes could still inhibit DENV-2 replication, suggesting that AuNPs maintained siRNA stability. Collectively, these results demonstrated that AuNPs were able to efficiently deliver siRNAs and control infection in vitro, indicating a novel anti-DENV strategy.

scholarly journals Cordycepin Inhibits Virus Replication in Dengue Virus-Infected Vero Cells

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3118
Author(s):  
Aussara Panya ◽  
Pucharee Songprakhon ◽  
Suthida Panwong ◽  
Kanyaluck Jantakee ◽  
Thida Kaewkod ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Rna Synthesis ◽  
Bioactive Compound ◽  
Vero Cells ◽  
Denv Infection ◽  
Severe Illness ◽  
Structural Protein ◽  
Half Maximal Effective Concentration ◽  
In Silico Molecular Docking ◽  
Important Enzyme

Dengue virus (DENV) infection causes mild to severe illness in humans that can lead to fatality in severe cases. Currently, no specific drug is available for the treatment of DENV infection. Thus, the development of an anti-DENV drug is urgently required. Cordycepin (3′-deoxyadenosine), which is a major bioactive compound in Cordyceps (ascomycete) fungus that has been used for centuries in Chinese traditional medicine, was reported to exhibit antiviral activity. However, the anti-DENV activity of cordycepin is unknown. We hypothesized that cordycepin exerts anti-DENV activity and that, as an adenosine derivative, it inhibits DENV replication. To test this hypothesis, we investigated the anti-DENV activity of cordycepin in DENV-infected Vero cells. Cordycepin treatment significantly decreased DENV protein at a half-maximal effective concentration (EC50) of 26.94 μM. Moreover, DENV RNA was dramatically decreased in cordycepin-treated Vero cells, indicating its effectiveness in inhibiting viral RNA replication. Via in silico molecular docking, the binding of cordycepin to DENV non-structural protein 5 (NS5), which is an important enzyme for RNA synthesis, at both the methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains, was predicted. The results of this study demonstrate that cordycepin is able to inhibit DENV replication, which portends its potential as an anti-dengue therapy.

scholarly journals Protein-protein interactions between A. aegypti midgut and dengue virus 2: two-hybrid screens using the midgut cDNA library

2015 ◽  
Vol 9 (12) ◽  
pp. 1338-1349 ◽  
Author(s):  
Hong-Wai Tham ◽  
Vinod R. M. T. Balasubramaniam ◽  
Miaw-Fang Chew ◽  
Hamdan Ahmad ◽  
Sharifah Syed Hassan
Keyword(s):  
Dengue Virus ◽  
Cdna Library ◽  
Protein Interactions ◽  
Biological Activities ◽  
Denv Infection ◽  
Peptidase Activity ◽  
Positive Outcomes ◽  
Insert Size ◽  
Oxidoreductase Activity ◽  
Two Hybrid

Introduction: Dengue virus (DENV) is principally transmitted by the Aedes aegypti mosquito. To date, mosquito population control remains the key strategy for reducing the continuing spread of DENV. The focus on the development of new vector control strategies through an understanding of the mosquito-virus relationship is essential, especially targeting the midgut, which is the first mosquito organ exposed to DENV infection. Methodology: A cDNA library derived from female adult A. aegypti mosquito midgut cells was established using the switching mechanism at the 5’ end of the RNA transcript (SMART), in combination with a highly potent recombination machinery of Saccharomyces cerevisiae. Gal4-based yeast two-hybrid (Y2H) assays were performed against DENV-2 proteins (E, prM, M, and NS1). Mammalian two-hybrid (M2H) and double immunofluorescence assays (IFA) were conducted to validate the authenticity of the three selected interactions. Results: The cDNA library was of good quality based on its transformation efficiency, cell density, titer, and the percentage of insert size. A total of 36 midgut proteins interacting with DENV-2 proteins were identified, some involved in nucleic acid transcription, oxidoreductase activity, peptidase activity, and ion binding. Positive outcomes were obtained from the three selected interactions validated using M2H and double IFA assays. Conclusions: The identified proteins have different biological activities that may aid in the virus replication pathway. Therefore, the midgut cDNA library is a valuable tool for identifying DENV-2 interacting proteins. The positive outcomes of the three selected proteins validated supported the quality of the cDNA library and the robustness of the Y2H mechanisms.

scholarly journals The Secreted Form of Dengue Virus Nonstructural Protein NS1 Is Endocytosed by Hepatocytes and Accumulates in Late Endosomes: Implications for Viral Infectivity

2005 ◽  
Vol 79 (17) ◽  
pp. 11403-11411 ◽  
Author(s):  
Sophie Alcon-LePoder ◽  
Marie-Thérèse Drouet ◽  
Pascal Roux ◽  
Marie-Pascale Frenkiel ◽  
Michel Arborio ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Mammalian Cells ◽  
Nonstructural Protein ◽  
Virus Production ◽  
Fluid Phase ◽  
Biological Properties ◽  
Late Endosomes ◽  
Huh7 Cells

ABSTRACT The flavivirus nonstructural protein NS1 is expressed as three discrete species in infected mammalian cells: an intracellular, membrane-associated form essential for viral replication, a cell surface-associated form that may be involved in signal transduction, and a secreted form (sNS1), the biological properties of which remain elusive. To determine the distribution of the dengue virus (DEN) sNS1 protein in vivo, we have analyzed by immunohistological means the tissue tropism of purified DEN sNS1 injected intravenously into adult mice. The sNS1 protein was found predominantly associated with the liver, where hepatocytes appeared to represent a major target cell. We further showed that sNS1 could be efficiently endocytosed by human Huh7 and HepG2 hepatocytes in vitro. After its internalization, the protein was detected intracellularly for at least 48 h without being substantially degraded. Colocalization studies of sNS1 with markers of the endolysosomal compartments revealed that the protein was specifically targeted to lysobisphosphatidic acid-rich structures reminiscent of late endosomes, as confirmed by electron microscopy. Intracellular accumulation of sNS1 in Huh7 cells enhanced the fluid phase uptake of rhodamine-labeled dextran. Furthermore, preincubation of Huh7 cells with sNS1 increased dengue virus production after infection with the homologous strain of DEN-1 virus. Our results demonstrate that the accumulation of DEN sNS1 in the late endosomal compartment of hepatocytes potentializes subsequent dengue virus infection in vitro, raising the possibility that sNS1 may contribute to viral propagation in vivo.

An experimental and theoretical approach to understand Fever, DENF & its cure

2020 ◽  
Vol 20 ◽  
Author(s):  
Vijay Kumar Vishvakarma ◽  
Ramesh Chandra ◽  
Prashant Singh
Keyword(s):  
Catalytic Activity ◽  
Dengue Virus ◽  
Theoretical Approach ◽  
Major Part ◽  
Genomic Structure ◽  
Denv Infection ◽  
Structural Proteins ◽  
Experimental Approaches ◽  
Ns3 Protease ◽  
Prime Target

: Fever is a response of human body due to an increase the temperature against the certain stimuli. It may be associated with several reasons and one of the major causes of fever is mosquito bite. Fever due to dengue virus (DENV) infection is being paid most attention out of several other fevers because of a large number of deaths reported worldwide. Dengue virus is transmitted by biting of the mosquitoes, Aedes aegypti and Aedes albopictus. DENV1, DENV2, DENV3 and DENV4 are the four serotypes of dengue virus and these serotypes have 65% similarities in their genomic structure. Genome of DENV is composed of single stranded RNA and it encodes for the polyprotein. Structural and non-structural proteins (nsP) are the two major part of protese. Researchers have paid high attention on the non-structural protease (nsP) of DENV like nsP1, nsP2A, nsP2B, nsP3, nsP4A, nsP4B and nsP5. The NS2B-NS3 protease of DENV is the prime target of the researchers as it is responsible for the catalytic activity. In the present time, Dengvaxia (vaccine) is being recommended to the patients suffering severely due to DENV infection in few countries only. Till date, neither a vaccine nor an effective medicine is available to combat with all four serotypes. This review describes the fever, its causes and studies to cure the infection due to DENV using theoretical and experimental approaches.

scholarly journals Potential Phosphorylation of Viral Nonstructural Protein 1 in Dengue Virus Infection

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1393
Author(s):  
Thanyaporn Dechtawewat ◽  
Sittiruk Roytrakul ◽  
Yodying Yingchutrakul ◽  
Sawanya Charoenlappanit ◽  
Bunpote Siridechadilok ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Nonstructural Protein ◽  
Antiviral Drug ◽  
Denv Infection ◽  
Site Directed Mutagenesis ◽  
Phosphorylation Sites ◽  
Post Translational Modification ◽  
Multifunctional Protein ◽  
Nonstructural Protein 1 ◽  
Underlying Mechanisms

Dengue virus (DENV) infection causes a spectrum of dengue diseases that have unclear underlying mechanisms. Nonstructural protein 1 (NS1) is a multifunctional protein of DENV that is involved in DENV infection and dengue pathogenesis. This study investigated the potential post-translational modification of DENV NS1 by phosphorylation following DENV infection. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), 24 potential phosphorylation sites were identified in both cell-associated and extracellular NS1 proteins from three different cell lines infected with DENV. Cell-free kinase assays also demonstrated kinase activity in purified preparations of DENV NS1 proteins. Further studies were conducted to determine the roles of specific phosphorylation sites on NS1 proteins by site-directed mutagenesis with alanine substitution. The T27A and Y32A mutations had a deleterious effect on DENV infectivity. The T29A, T230A, and S233A mutations significantly decreased the production of infectious DENV but did not affect relative levels of intracellular DENV NS1 expression or NS1 secretion. Only the T230A mutation led to a significant reduction of detectable DENV NS1 dimers in virus-infected cells; however, none of the mutations interfered with DENV NS1 oligomeric formation. These findings highlight the importance of DENV NS1 phosphorylation that may pave the way for future target-specific antiviral drug design.

scholarly journals Unveiling Biological Activities of Marine Fungi: The Effect of Sea Salt

2021 ◽  
Vol 11 (13) ◽  
pp. 6008
Author(s):  
Micael F. M. Gonçalves ◽  
Ana Paço ◽  
Luís F. Escada ◽  
Manuela S. F. Albuquerque ◽  
Carlos A. Pinto ◽  
...  
Keyword(s):  
Marine Fungi ◽  
Culture Media ◽  
Biological Activities ◽  
Vero Cells ◽  
Growth Conditions ◽  
Sea Salt ◽  
Cytotoxic Activities ◽  
Methanolic Extracts ◽  
Assisted Extraction ◽  
Multiresistant Strains

There is an urgent need for new substances to overcome current challenges in the health sciences. Marine fungi are known producers of numerous compounds, but the manipulation of growth conditions for optimal compound production can be laborious and time-consuming. In Portugal, despite its very long coastline, there are only a few studies on marine fungi. From a collection of Portuguese marine fungi, we screened for antimicrobial, antioxidant, enzymatic, and cytotoxic activities. Mycelia aqueous extracts, obtained by high pressure-assisted extraction, and methanolic extracts of culture media showed high antioxidant, antimicrobial, and cytotoxic activities. The mycelium extracts of Cladosporium rubrum showed higher antioxidant potential compared to extracts from other fungi. Mycelia and culture media extracts of Aspergillus affinis and Penicillium lusitanum inhibited the growth of Staphylococcus aureus, Kocuria rhizophila, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, including multiresistant strains. Penicillium lusitanum and Trichoderma aestuarinum inhibited the growth of clinical strains of Candida albicans, C. glabrata, C. parapsilosis, and C. tropicalis. All extracts from culture media were cytotoxic to Vero cells. Sea salt induced alterations in the mycelium’s chemical composition, leading to different activity profiles.

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