scholarly journals Diterpenes/Diterpenoids and Their Derivatives as Potential Bioactive Leads against Dengue Virus: A Computational and Network Pharmacology Study

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6821
Author(s):  
Rasel Ahmed Khan ◽  
Rajib Hossain ◽  
Abolghasem Siyadatpanah ◽  
Khattab Al-Khafaji ◽  
Abul Bashar Ripon Khalipha ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Dengue Fever ◽  
Computational Study ◽  
Viral Proteins ◽  
Network Pharmacology ◽  
Binding Affinities ◽  
Ns1 Protein ◽  
Structural Protein ◽  
E Protein

Dengue fever is a dangerous infectious endemic disease that affects over 100 nations worldwide, from Africa to the Western Pacific, and is caused by the dengue virus, which is transmitted to humans by an insect bite of Aedes aegypti. Millions of citizens have died as a result of dengue fever and dengue hemorrhagic fever across the globe. Envelope (E), serine protease (NS3), RNA-directed RNA polymerase (NS5), and non-structural protein 1 (NS1) are mostly required for cell proliferation and survival. Some of the diterpenoids and their derivatives produced by nature possess anti-dengue viral properties. The goal of the computational study was to scrutinize the effectiveness of diterpenoids and their derivatives against dengue viral proteins through in silico study. Methods: molecular docking was performed to analyze the binding affinity of compounds against four viral proteins: the envelope (E) protein, the NS1 protein, the NS3 protein, and the NS5 protein. Results: among the selected drug candidates, triptolide, stevioside, alepterolic acid, sphaeropsidin A, methyl dodovisate A, andrographolide, caesalacetal, and pyrimethamine have demonstrated moderate to good binding affinities (−8.0 to −9.4 kcal/mol) toward the selected proteins: E protein, NS3, NS5, and NS1 whereas pyrimethamine exerts −7.5, −6.3, −7.8, and −6.6 kcal/mol with viral proteins, respectively. Interestingly, the binding affinities of these lead compounds were better than those of an FDA-approved anti-viral medication (pyrimethamine), which is underused in dengue fever. Conclusion: we can conclude that diterpenoids can be considered as a possible anti-dengue medication option. However, in vivo investigation is recommended to back up the conclusions of this study.

scholarly journals Development of Bacteriophage Virus-Like Particle Vaccines Displaying Conserved Epitopes of Dengue Virus Non-Structural Protein 1

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 726
Author(s):  
Nikole L. Warner ◽  
Kathryn M. Frietze
Keyword(s):  
Dengue Virus ◽  
Population Based ◽  
Ns1 Protein ◽  
Structural Protein ◽  
Denv Serotypes ◽  
Conserved Regions ◽  
Virus Like Particle ◽  
Dependent Cell ◽  
Infected Cells ◽  
Plasma Leakage

Dengue virus (DENV) is a major global health problem, with over half of the world’s population at risk of infection. Despite over 60 years of efforts, no licensed vaccine suitable for population-based immunization against DENV is available. Here, we describe efforts to engineer epitope-based vaccines against DENV non-structural protein 1 (NS1). NS1 is present in DENV-infected cells as well as secreted into the blood of infected individuals. NS1 causes disruption of endothelial cell barriers, resulting in plasma leakage and hemorrhage. Immunizing against NS1 could elicit antibodies that block NS1 function and also target NS1-infected cells for antibody-dependent cell cytotoxicity. We identified highly conserved regions of NS1 from all four DENV serotypes. We generated synthetic peptides to these regions and chemically conjugated them to bacteriophage Qβ virus-like particles (VLPs). Mice were immunized two times with the candidate vaccines and sera were tested for the presence of antibodies that bound to the cognate peptide, recombinant NS1 from all four DENV serotypes, and DENV-2-infected cells. We found that two of the candidate vaccines elicited antibodies that bound to recombinant NS1, and one candidate vaccine elicited antibodies that bound to DENV-infected cells. These results show that an epitope-specific vaccine against conserved regions of NS1 could be a promising approach for DENV vaccines or therapeutics to bind circulating NS1 protein.

scholarly journals Potential of Peptide-Based Non-Structural Protein 1 (NS1) Inhibitor in Obstructing Dengue Virus (DENV) Replication

2021 ◽  
Vol 3 (1) ◽  
pp. 1-12
Author(s):  
Muhammad Mikail Athif Zhafir Asyura ◽  
Ahmad Fauzi ◽  
Fakhru Adlan Ayub
Keyword(s):  
Dengue Virus ◽  
Viral Replication ◽  
Dengue Fever ◽  
Immune Cells ◽  
Viral Protein ◽  
Viral Genome ◽  
Antiviral Drug ◽  
Ns1 Protein ◽  
Humoral Immune ◽  
Stimulation Of

Introduction: Dengue Virus (DENV) is the pathogen for human dengue fever and is responsible for 390 million infections per year. The viral genome produces about 10 viral protein products, one of them being NS1. The NS1 protein plays a key role in viral replication and stimulation of humoral immune cells, thus being the perfect candidate to create an effective antiviral drug or vaccine for dengue Methods: Dengue Virus (DENV) is the pathogen for human dengue fever and is responsible for 390 million infections per year. The viral genome produces about 10 viral protein products, one of them being NS1. The NS1 protein plays a key role in viral replication and stimulation of humoral immune cells, thus being the perfect candidate to create an effective antiviral drug or vaccine for dengue Conclusion: The review established promising results of using peptide-based intervention on NS1. Further in vivo and randomized controlled trials are advised to solidify the applicability and biosafety of the intervention    

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 The dengue virus non-structural protein 1 (NS1) use the scavenger receptor B1 as cell receptor in human hepatic and mosquito cells

2019 ◽  
Author(s):  
Ana C. Alcalá ◽  
José L. Maravillas ◽  
David Meza ◽  
Octavio T. Ramirez ◽  
Juan E. Ludert ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Virus Disease ◽  
Scavenger Receptor ◽  
Direct Interaction ◽  
Cell Receptor ◽  
Serum Lipoprotein ◽  
Structural Protein ◽  
Surface Binding

AbstractDengue is the most common virus disease transmitted to humans by mosquitoes. The dengue virus NS1 is a multifunctional protein that form part of replication complexes. In addition, NS1 is also secreted, as a hexamer, to the extracellular milieu. Circulating NS1 has been associated with dengue pathogenesis by several different mechanisms. Cell binding and internalization of soluble NS1 result in the disruption of tight junctions and in down regulation of the innate immune response. In this work, we report that the HDL scavenger receptor B1 (SRB1) in human hepatic cells, and a scavenger receptor B1-like in mosquito C6/36 cells act as cell surface binding receptor for dengue virus NS1. The presence of the SRB1 on the plasma membrane of C6/36 cells, as well as in Huh-7 cells, was demonstrated by confocal microcopy. Internalization of NS1 can be efficiently blocked by anti-SRB1 antibodies and previous incubation of the cells with HDL significantly reduces NS1 internalization. In addition, the transient expression of SRB1 in Vero cells, which lack the receptor, renders these cells susceptible to NS1 entry. Direct interaction between soluble NS1 and the SRB1 in Huh7 and C6/36 cells was demonstrated in vivo by proximity ligation assays an in vitro by surface plasmon resonance. Finally, data is presented indicating that the SRB1 also act as cell receptor for zika virus NS1. These results demonstrate that dengue virus NS1, a bona fide lipoprotein, usurps the HDL receptor for cell entry and offers explanations for the altered serum lipoprotein homeostasis observed in dengue patients.

scholarly journals Immunogenicity of Recombinant DNA Vaccine Encoding Non-Structural Protein-1 Dengue Virus Serotype-2 in Balb/c Mice

2021 ◽  
Vol 15 (2) ◽  
pp. 4
Author(s):  
Elitha Pulungan
Keyword(s):  
Immune Response ◽  
Dengue Virus ◽  
Dna Vaccine ◽  
Humoral Immune Response ◽  
Structural Proteins ◽  
Ns1 Protein ◽  
Structural Protein ◽  
Humoral Immune ◽  
Virus Serotype ◽  
Positive Strand Rna

Background: Dengue Hemorrhagic Fever (DHF) is an infectious disease caused by the dengue virus (DENV) which spread widely in tropical and subtropical regions of the world. DENV is a single-positive strand RNA virus with a genome size of ± 11kb which encodes three structural proteins, seven non-structural proteins, and two untranslated regions (UTR). The non-structural protein-1 (NS1) of DENV is known to have important role in dengue pathogenesis also promising to be developed as dengue vaccine. Lately, novel vaccine approach by DNA immunization have given new perspective for a safe, stable, and immunogenic vaccine platform. Previously, we have successfully construct DNA vaccine encoding NS1 protein of DENV2 (pUNS1) which express recombinant NS1 protein in-vitro. Thus, in this current study the ability of pUNS1 to induce humoral immune response will be further analyzed by in mice immunization. Methods: Sixteen BALB/c mice aged of 4 weeks were immunized 3 times with 100 µg of pUNS1 or pUMVC4a on 2 week time interval. Blood sampling was carried out just before immunization and termination was done 2 week after last immunization. Titer from individual mice sera against DENV-2 were measure with in-house ELISA. Results: IgG against NS1 protein of DENV2 titer from mice group immunized with recombinant pUNS1 shown high ELISA absorbancies, 5 times higher than pUMVC4a group. This result suggest the ability of pUNS1 to induce humoral immune response against NS1 DENV-2 in-vivo. Conclusion: Recombinant pUNS1 can induce humoral immune response in mice.

scholarly journals Docking study of Selected Vinis vitifera seeds constituents on Dengue viral proteins – An In Silico approach

2018 ◽  
Vol 6 (04) ◽  
pp. 25-31
Author(s):  
M. Bhavya ◽  
M. Ramya ◽  
N. Nagarjun ◽  
Nagarathna Amresh ◽  
Balasubramanian Sathyamurthy
Keyword(s):  
Virtual Screening ◽  
Dengue Virus ◽  
In Silico ◽  
Viral Proteins ◽  
Docking Study ◽  
Virus Protein ◽  
Binding Affinities ◽  
Amino Acid Residues ◽  
Protein Targets ◽  
Docking Approach

Dengue is a mosquito-borne systemic viral infection caused by any of the four antigenically related dengue viruses (DENV).The dengue virus belongs to the Flaviviridae family of viruses that cause diseases in humans.A virtual screening analysis of phytochemical structures with dengue virus protein targets has been carried out using a molecular docking approach with vins vinifera seeds. Grapes (Vinis vitifera) are believed to have health benefits due to their antioxidant activity and polyphenols. In this study we examined the binding affinities of 14 ligands with seven non structural Dengu viral proteins through In Silico methods like virtual screening and docking process which showed that compound F and compound N had high binding efficiencies with these proteins along with the type of hydrogen bonds and their respective amino acid residues at their docked sites.

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 Alanine substitutions within a linker region of the influenza A virus non-structural protein 1 alter its subcellular localization and attenuate virus replication

2011 ◽  
Vol 92 (8) ◽  
pp. 1832-1842 ◽  
Author(s):  
Wei Li ◽  
James W. Noah ◽  
Diana L. Noah
Keyword(s):  
Virus Infection ◽  
Subcellular Localization ◽  
Influenza A Virus ◽  
Influenza A ◽  
Mdck Cells ◽  
Ns1 Protein ◽  
Structural Protein ◽  
Apoptotic Pathway ◽  
Linker Region

The influenza A virus non-structural protein 1 (NS1) is a multifunctional protein and an important virulence factor. It is composed of two well-characterized domains linked by a short, but not well crystallographically defined, region of unknown function. To study the possible function of this region, we introduced alanine substitutions to replace the two highly conserved leucine residues at amino acid positions 69 and 77. The mutant L69,77A NS1 protein retained wild-type (WT)-comparable binding capabilities to dsRNA, cleavage and polyadenylation specificity factor 30 and the p85β subunit of PI3K. A mutant influenza A virus expressing the L69,77A NS1 protein was generated using reverse genetics. L69,77A NS1 virus infection induced significantly higher levels of beta interferon (IFN-β) expression in Madin–Darby canine kidney (MDCK) cells compared with WT NS1 virus. In addition, the replication rate of the L69,77A NS1 virus was substantially lower in MDCK cells but not in Vero cells compared with the WT virus, suggesting that the L69,77A NS1 protein does not fully antagonize IFN during viral replication. L69,77A NS1 virus infection was not able to activate the PI3K/Akt anti-apoptotic pathway, suggesting that the mutant NS1 protein may not be localized such that it has access to p85β in vivo during infection, which was supported by the altered subcellular localization pattern of the mutant NS1 compared with WT NS1 after transfection or virus infection. Our data demonstrate that this linker region between the two domains is critical for the functions of the NS1 protein during influenza A virus infection, possibly by determining the protein’s correct subcellular localization.

scholarly journals OVERVIEW OF NUCLEAR FACTOR-KB (NF-KB) AND NON-STRUCTURAL PROTEIN 1 (NS1) IN PATIENTS WITH DENGUE FEVER IN PREMIER HOSPITAL, SURABAYA

2019 ◽  
Vol 7 (5) ◽  
pp. 109
Author(s):  
Ni Nyoman Budiutari ◽  
Yoes Prijatna Dachlan ◽  
Jusak Nugraha
Keyword(s):  
Transcription Factors ◽  
Viral Replication ◽  
Dengue Fever ◽  
Interleukin 1 ◽  
Dengue Infection ◽  
Sandwich Elisa ◽  
Rapid Test ◽  
Host Cells ◽  
Ns1 Protein ◽  
Structural Protein

Dengue fever (DF) is an acute viral fever caused by RNA virus that is transmitted by Aedes aegypti and Aedes albopictus mosquitoes. DF is also called viral arthropod-borne disease and is accompanied by headaches, joint and muscle pain. The main target of dengue infection is macrophages or monocytes and dendritic cells (DC). Infected DC is caused the viral replication and the endocytosis into endosomal, easier, thus inducing the activation of NF-ĸB transcription factor to produce proinflammatory cytokines such as Tumor Necrosis Factor-α (TNF-α), Interleukin-1 (IL-1), IL-6, IL-12 and chemokine. NF-kB is one of the transcription factors involved in the regulation of the expression of various cytokines, chemokines and anti/pro-apoptotic proteins during infection and act as indicator of disease severity. Infected DC cells are secreted NS1 protein which is the co-factor needed for viral replication and can be detected in the first eight days. The level will be higher in the initial phase of fever. The purpose of this study was to analyze the description of NF-kB and NS1 levels in the serum of patients with dengue fever through observational analytic studies through a cross-sectional approach. This study was done on 40 patients with dengue fever and 10 healthies people as negative controls. NS1 was analyzed in serum of Panbio rapid test and NF-kB level were measured by sandwich ELISA. The results are showed positive and negative NS1 results in dengue fever patients. The average NF-kB serum level in dengue fever patients was found to be higher than the control. NF-ĸB level in negative NS1 was higher than the NS1 positive group. It is showed that NS1 is detected both in the acute phase. The detection of NF-ĸB is showed the involvement of transcription factors in the development of dengue virus infection and has a protective role for host cells.

In Vitro and In Vivo Stability of P884T, a Mutation that Relocalizes Dengue Virus 2 Non-structural Protein 5

2021 ◽  
Author(s):  
Colin X. Cheng ◽  
Min Jie Alvin Tan ◽  
Kitti W. K. Chan ◽  
Satoru Watanabe ◽  
Sai Wang ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Structural Protein
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