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 Studi in Silico Lima Senyawa Aktif Sebagai Penghambat Protein Virus Dengue

2019 ◽  
pp. 40-47
Author(s):  
Reni Herman
Keyword(s):  
Dengue Virus ◽  
In Silico ◽  
Dengue Infection ◽  
Epigallocatechin Gallate ◽  
Denv Infection ◽  
Virus Protein ◽  
Structural Protein ◽  
The Stability ◽  
The Tropics ◽  
Ns3 Protease

Dengue infection is an endemic disease in the tropics and subtropics, caused by dengue virus (DENV) infection. Some compounds have been shown to have antiviral effects on some viruses. In silico study is conducted to predict the stability of natural ingredient compounds: artemisinin, catechin, mangiferin, epigallocatechin gallate (EGCG), and quercetin in their interactions with dengue virus proteins at molecular level. This study is carried out using the 2008 version of the Molecular Operating Environment (MOE) software. Ligands are ribavirin as antiviral control whereas artemisinin, mangiferin, EGCG, and quercetin with 3D mole format structures. The downloaded DENV protein with PDB document format is the DENV serotype 2 envelope protein with 1OKE code, non structural protein 3 (NS3) with 2VBC code and NS5 protein with 1L9K code. In silico test generally showed that catechin, mangiferin, EGCG, and quercetin had more stable docking ligands to DENV’s proteins. In particular, mangiferin had stable docking ligand to envelope proteins, NS3 (helicase and protease) and in NS5-methyltransferase compared to ribavirin. Catechin stabled on NS3-protease, EGCG on NS3 (helicase and protease) and quercetin on NS3-protease. Artemisinin had less stabled bonds than ribavirin. The results indicated that catechin, mangiferin, EGCG, and quercetin had potential inhibition to DENV proteins whereas mangiferin was the most potential compound to inhibit dengue virus protein targets.

scholarly journals Development of a Dengue Virus Serotype-Specific Non-Structural Protein 1 Capture Immunochromatography Method

Sensors ◽  
2021 ◽  
Vol 21 (23) ◽  
pp. 7809
Author(s):  
Kanaporn Poltep ◽  
Emi E. Nakayama ◽  
Tadahiro Sasaki ◽  
Takeshi Kurosu ◽  
Yoshiki Takashima ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Pcr Amplification ◽  
Denv Infection ◽  
Epidemiologic Studies ◽  
Cross Reaction ◽  
Structural Protein ◽  
Current Standard ◽  
Denv Serotypes ◽  
Detection Systems ◽  
Virus Serotype

Four serotypes of dengue virus (DENV), type 1 to 4 (DENV-1 to DENV-4), exhibit approximately 25–40% of the difference in the encoded amino acid residues of viral proteins. Reverse transcription of RNA extracted from specimens followed by PCR amplification is the current standard method of DENV serotype determination. However, since this method is time-consuming, rapid detection systems are desirable. We established several mouse monoclonal antibodies directed against DENV non-structural protein 1 and integrated them into rapid DENV detection systems. We successfully developed serotype-specific immunochromatography systems for all four DENV serotypes. Each system can detect 104 copies/mL in 15 min using laboratory and clinical isolates of DENV. No cross-reaction between DENV serotypes was observed in these DENV isolates. We also confirmed that there was no cross-reaction with chikungunya, Japanese encephalitis, Sindbis, and Zika viruses. Evaluation of these systems using serum from DENV-infected individuals indicated a serotype specificity of almost 100%. These assay systems could accelerate both DENV infection diagnosis and epidemiologic studies in DENV-endemic areas.

scholarly journals Salivary Detection of Dengue Virus NS1 Protein with a Label-Free Immunosensor for Early Dengue Diagnosis

Sensors ◽  
2018 ◽  
Vol 18 (8) ◽  
pp. 2641 ◽  
Author(s):  
Daniel Wasik ◽  
Ashok Mulchandani ◽  
Marylynn Yates
Keyword(s):  
Early Diagnosis ◽  
Dengue Virus ◽  
Dengue Infection ◽  
Denv Infection ◽  
Human Saliva ◽  
Diagnostic Methods ◽  
Label Free ◽  
Ns1 Protein ◽  
Structural Protein ◽  
Blood Draw

Dengue virus (DENV) is a highly pathogenic, arthropod-borne virus transmitted between people by Aedes mosquitoes. Despite efforts to prevent global spread, the potential for DENV epidemics is increasing world-wide. Annually, 3.6 billion people are at risk of infection. With no licensed vaccine, early diagnosis of dengue infection is critical for clinical management and patient survival. Detection of DENV non-structural protein 1 (NS1) is a clinically accepted biomarker for the early detection of DENV infection. Unfortunately, virtually all of the laboratory and commercial DENV NS1 diagnostic methods require a blood draw for sample analysis, limiting point-of-care diagnostics and decreases patient willingness. Alternatively, NS1 in human saliva has been identified for the potential early diagnosis of DENV infection. The collection of saliva is simple, non-invasive, painless, and inexpensive, even by minimally trained personnel. In this study, we present a label-free chemiresistive immunosensor for the detection of the DENV NS1 protein utilizing a network of single-walled carbon nanotubes functionalized with anti-dengue NS1 monoclonal antibodies. NS1 was successfully detected in adulterated artificial human saliva over the range of clinically relevant concentrations with high sensitivity and selectivity. It has potential application in clinical diagnosis and the ease of collection allows for self-testing, even within the home.

scholarly journals A Novel Role for the Regulatory Nod-Like Receptor NLRP12 in Anti-Dengue Virus Response

2021 ◽  
Vol 12 ◽  
Author(s):  
Xingyu Li ◽  
Zhuo Dong ◽  
Yan Liu ◽  
Weifeng Song ◽  
Jieying Pu ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Denv Infection ◽  
Poly I:C ◽  
Severe Illness ◽  
Human Macrophage ◽  
Type I ◽  
Zikv Infection ◽  
Type I Ifns

Dengue Virus (DENV) infection can cause severe illness such as highly fatality dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Innate immune activation by Nod-like receptors (NLRs) is a critical part of host defense against viral infection. Here, we revealed a key mechanism of NLRP12-mediated regulation in DENV infection. Firstly, NLRP12 expression was inhibited in human macrophage following DENV or other flaviviruses (JEV, YFV, ZIKV) infection. Positive regulatory domain 1 (PRDM1) was induced by DENV or poly(I:C) and suppressed NLRP12 expression, which was dependent on TBK-1/IRF3 and NF-κB signaling pathways. Moreover, NLRP12 inhibited DENV and other flaviviruses (JEV, YFV, ZIKV) replication, which relied on the well-conserved nucleotide binding structures of its NACHT domain. Furthermore, NLRP12 could interact with heat shock protein 90 (HSP90) dependent on its Walker A and Walker B sites. In addition, NLRP12 enhanced the production of type I IFNs (IFN-α/β) and interferon-stimulated genes (ISGs), including IFITM3, TRAIL and Viperin. Inhibition of HSP90 with 17-DMAG impaired the upregulation of type I IFNs and ISGs induced by NLRP12. Taken together, we demonstrated a novel mechanism that NLRP12 exerted anti-viral properties in DENV and other flaviviruses (JEV, YFV, ZIKV) infection, which brings up a potential target for the treatment of DENV infection.

scholarly journals Horseradish peroxidase-labeled rabbit anti-non-structural protein 1 of dengue virus-2 for the diagnosis of dengue virus infections

2019 ◽  
Vol 28 (2) ◽  
pp. 103-9
Author(s):  
Evy Suryani Arodes ◽  
Beti Ernawati Dewi ◽  
Tjahjani Mirawati Sudiro
Keyword(s):  
Early Diagnosis ◽  
Horseradish Peroxidase ◽  
Dengue Virus ◽  
Periodate Oxidation ◽  
Denv Infection ◽  
Negative Control ◽  
Enzyme Linked Immunosorbent Assay ◽  
Ns1 Protein ◽  
Structural Protein ◽  
Ns1 Antigen

BACKGROUND Early diagnosis of dengue virus (DENV) infection is essential for patient management and disease control. Detection of the antigen non-structural protein 1 (NS1) has been proven to provide early diagnosis of DENV infection. Thus, commercial NS1 antigen detection assays have been increasingly used and are becoming thetool of choice among clinicians to confirm DENV infection in Indonesia. METHODS To obtain anti-NS1 DENV antibody, NS1 protein (90 µg/ml) from the collection of the Department of Microbiology, Faculty of Medicine, Universitas Indonesia was injected into a rabbit. The anti-NS1 antibody from the rabbit was then labeled with horseradish peroxidase (HRP) using the periodate oxidation method. Sera were tested by enzyme-linked immunosorbent assay (ELISA) to detect NS1 from DENV-infected patients. RESULTS Serially diluted antibody labeled with HRP tested using the direct ELISA method showed the highest absorbance value at a 1:100 dilution (Mean [SD] = 1.35 [0.35]); even at a dilution as high as 1:3,200 (0.22 [0.15]), antibody labeled with HRP was able to detect the NS1 protein, although the absorbance value did not differ greatly from that of the negative control (0.13 [0.01]). CONCLUSIONS In an attempt to develop an NS1-based diagnostic test, polyclonal anti-NS1 DENV antibody was successfully produced as a diagnostic assay to determine the presence of DENV NS1 antigen in patients’ sera.

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 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 The dengue virus non-structural protein 1 (NS1) interacts with the putative epigenetic regulator DIDO1 to promote flavivirus replication.

2021 ◽  
Author(s):  
gerson caraballo ◽  
Romel Rosales ◽  
Mercedes Viettri ◽  
Siyuan Ding ◽  
Harry B Greenberg ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Viral Replication ◽  
Ribosomal Proteins ◽  
Denv Infection ◽  
Structural Protein ◽  
Transcription Analysis ◽  
Multifunctional Protein ◽  
Rna Surveillance ◽  
Mosquito Cells ◽  
Expression Pathways

Dengue virus (DENV) NS1 is a multifunctional protein essential for viral replication. To gain insights into NS1 functions in mosquito cells, the protein interactome of DENV NS1 in C6/36 cells was investigated using a proximity biotinylation system and mass spectrometry. Approximately 14% of the 817 identified proteins coincide with interactomes obtained in vertebrate cells, including ontology groups of the oligosaccharide transferase complex, the chaperonin containing TCP-1, and nuclear import and export, vesicle localization and ribosomal proteins. Notably, other protein pathways such as epigenetic regulation and RNA silencing, not previously reported in vertebrate cells, were also found in the NS1 interactome in mosquito cells. Due to the novel interaction observed for NS1 and DIDO1 (Death Inducer-Obliterator 1), we further explored the role of DIDO1 in viral replication. Interactions between NS1 and DIDO1were corroborated in infected C6/36 and Aag2 cells, by colocalization and proximity ligation assays. Silencing DIDO1 expression in C6/36 and Aag2 cells results in a significant reduction in DENV and ZIKV replication and progeny production. Comparison of transcription analysis of mock or DENV infected C6/36 silenced for DIDO1, revealed variations in multiple gene expression pathways, including pathways associated with DENV infection such as RNA surveillance, IMD and Toll. These results suggest that DIDO1 is a host factor involved in the negative modulation of the antiviral response and necessary for flavivirus replication. Our findings uncover novel mechanisms of NS1 to promote DENV and ZIKV replication and add to the understanding of NS1 as a multifunctional protein.

Structure and Function of the Non-Structural Protein of Dengue Virus and its Applications in Antiviral Therapy

2016 ◽  
Vol 17 (3) ◽  
pp. 371-380 ◽  
Author(s):  
Qian Xie ◽  
Bao Zhang ◽  
JianHai Yu ◽  
Qinghua Wu ◽  
Fangji Yang ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Antiviral Therapy ◽  
Structure And Function ◽  
Structural Protein ◽  
And Function

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.

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