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Dengue Literature - Latest PubMed Articles

Overview of latest articles and publications on ebola in PubMed. PubMed is a service of the US National Library of Medicine that includes over 18 million citations from MEDLINE and other life science journals.


  • Viral pathogenesis: Dengue virus takes on cGAS.
    Viral pathogenesis: Dengue virus takes on cGAS. [Journal Article]Nat Microbiol 2017 Mar 27.:17050.NMvan Gent M, Gack MU Publisher Full Text

  • Dengue virus NS2B protein targets cGAS for degradation and prevents mitochondrial DNA sensing during infection.
    Dengue virus NS2B protein targets cGAS for degradation and prevents mitochondrial DNA sensing during infection. [Journal Article]Nat Microbiol 2017 Mar 27.:17037.NMAguirre S, Luthra P, Sanchez-Aparicio MT, et al. During the last few decades, the global incidence of dengue virus (DENV) has increased dramatically, and it is now endemic in more than 100 countries. To establish a productive infection in humans, DEN...Publisher Full TextDuring the last few decades, the global incidence of dengue virus (DENV) has increased dramatically, and it is now endemic in more than 100 countries. To establish a productive infection in humans, DENV uses different strategies to inhibit or avoid the host innate immune system. Several DENV proteins have been shown to strategically target crucial components of the type I interferon system. Here, we report that the DENV NS2B protease cofactor targets the DNA sensor cyclic GMP-AMP synthase (cGAS) for lysosomal degradation to avoid the detection of mitochondrial DNA during infection. Such degradation subsequently results in the inhibition of type I interferon production in the infected cell. Our data demonstrate a mechanism by which cGAS senses cellular damage upon DENV infection.

  • Crystal structure of Zika virus NS5 RNA-dependent RNA polymerase.
    Crystal structure of Zika virus NS5 RNA-dependent RNA polymerase. [Journal Article]Nat Commun 2017 Mar 27.:14764.NCGodoy AS, Lima GM, Oliveira KI, et al. The current Zika virus (ZIKV) outbreak became a global health threat of complex epidemiology and devastating neurological impacts, therefore requiring urgent efforts towards the development of novel ef...Publisher Full TextThe current Zika virus (ZIKV) outbreak became a global health threat of complex epidemiology and devastating neurological impacts, therefore requiring urgent efforts towards the development of novel efficacious and safe antiviral drugs. Due to its central role in RNA viral replication, the non-structural protein 5 (NS5) RNA-dependent RNA-polymerase (RdRp) is a prime target for drug discovery. Here we describe the crystal structure of the recombinant ZIKV NS5 RdRp domain at 1.9 Å resolution as a platform for structure-based drug design strategy. The overall structure is similar to other flaviviral homologues. However, the priming loop target site, which is suitable for non-nucleoside polymerase inhibitor design, shows significant differences in comparison with the dengue virus structures, including a tighter pocket and a modified local charge distribution.

  • Clinical Features of Patients with Zika and dengue virus co-infection in Singapore.
    Clinical Features of Patients with Zika and dengue virus co-infection in Singapore. [Letter]J Infect 2017 Mar 23.JIChia PY, Yew HS, Ho H, et al. Publisher Full Text

  • Discovering key residues of dengue virus NS2b-NS3-protease: New binding sites for antiviral inhibitors design.
    Discovering key residues of dengue virus NS2b-NS3-protease: New binding sites for antiviral inhibitors design. [Journal Article]Biochem Biophys Res Commun 2017 Mar 23.BBAguilera-Pesantes D, Robayo LE, Méndez PE, et al. The NS2B-NS3 protease is essential for the Dengue Virus (DENV) replication process. This complex constitutes a target for efficient antiviral discovery because a drug could inhibit the viral polyprotei...Publisher Full TextThe NS2B-NS3 protease is essential for the Dengue Virus (DENV) replication process. This complex constitutes a target for efficient antiviral discovery because a drug could inhibit the viral polyprotein processing. Furthermore, since the protease is highly conserved between the four Dengue virus serotypes, it is probable that a drug would be equally effective against all of them. In this article, a strategy is reported that allowed us to identify influential residues on the function of the Dengue NS2b-NS3 Protease. Moreover, this is a strategy that could be applied to virtually any protein for the search of alternative influential residues, and for non-competitive inhibitor development. First, we incorporated several features derived from computational alanine scanning mutagenesis, sequence, structure conservation, and other structure-based characteristics. Second, these features were used as variables to obtain a multilayer perceptron model to identify defined groups (clusters) of key residues as possible candidate pockets for binding sites of new leads on the DENV protease. The identified residues included: i) amino acids close to the beta sheet-loop-beta sheet known to be important in its closed conformation for NS2b ii) residues close to the active site, iii) several residues evenly spread on the NS2b-NS3 contact surface, and iv) some inner residues most likely related to the overall stability of the protease. In addition, we found concordance on our list of residues with previously identified amino acids part of a highly conserved peptide studied for vaccine development.

  • Curcumin inhibits Zika and chikungunya virus infection by inhibiting cell binding.
    Curcumin inhibits Zika and chikungunya virus infection by inhibiting cell binding. [Journal Article]Antiviral Res 2017 Mar 23.ARMounce BC, Cesaro T, Carrau L, et al. Several compounds extracted from spices and herbs exhibit antiviral effects in vitro, suggesting potential pharmacological uses. Curcumin, a component of turmeric, has been used as a food additive and ...Publisher Full TextSeveral compounds extracted from spices and herbs exhibit antiviral effects in vitro, suggesting potential pharmacological uses. Curcumin, a component of turmeric, has been used as a food additive and herbal supplement due to its potential medicinal properties. Previously, curcumin exhibited antiviral properties against several viruses, including dengue virus and hepatitis C virus, among others. Here, we describe the antiviral effect of curcumin on Zika and chikungunya viruses, two mosquito-borne outbreak viruses. Both viruses responded to treatment of cells with up to 5 μM curumin without impacting cellular viability. We observed that direct treatment of virus with curcumin reduced infectivity of virus in a dose- and time-dependent manner for these enveloped viruses, as well as vesicular stomatitis virus. In contrast, we found no change in infectivity for Coxsackievirus B3, a non-enveloped virus. Derivatives of curcumin also exhibited antiviral activity against enveloped viruses. Further examination revealed that curcumin interfered with the binding of the enveloped viruses to cells in a dose-dependent manner, though the integrity of the viral RNA was maintained. Together, these results expand the family of viruses sensitive to curcumin and provide a mechanism of action for curcumin's effect on these enveloped viruses.

  • Increased activity of unlinked Zika virus NS2B/NS3 protease compared to linked Zika virus protease.
    Increased activity of unlinked Zika virus NS2B/NS3 protease compared to linked Zika virus protease. [Journal Article]Biochem Biophys Res Commun 2017 Mar 22.BBKuiper BD, Slater K, Spellmon N, et al. Zika virus (ZIKV) is a flavivirus spread by daytime-active Aedes spp. mosquitoes such as A. aegypti and A. albopictus. Previously thought to be a mild infection, the latest ZIKV outbreak in the America...Publisher Full TextZika virus (ZIKV) is a flavivirus spread by daytime-active Aedes spp. mosquitoes such as A. aegypti and A. albopictus. Previously thought to be a mild infection, the latest ZIKV outbreak in the Americas is causally associated with more severe symptoms as well as severe birth defects, such as microcephaly. Currently no vaccine or antiviral exists. However, recent progress has demonstrated the viral NS2B/NS3 protease may be a suitable target for the development of small-molecule antiviral agents. To better understand the ZIKV protease, we expressed, purified, and characterized unlinked and linked NS2B/NS3 protease corresponding to an isolate from the recent outbreak in Puerto Rico. Unlinked ZIKV protease is more active and binds substrate with greater affinity than linked ZIKV protease. Therefore, we propose that unlinked ZIKV protease be used when evaluating or designing ZIKV protease inhibitors. Additionally, potent inhibitors of related viral proteases, like West Nile Virus and Dengue virus, may serve as advanced starting points to identify and develop ZIKV protease inhibitors.

  • Novel synthesis of gold nanoparticles using Artemisia vulgaris L. leaf extract and their efficacy of larvicidal activity against dengue fever vector Aedes aegypti L.
    Novel synthesis of gold nanoparticles using Artemisia vulgaris L. leaf extract and their efficacy of larvicidal activity against dengue fever vector Aedes aegypti L. [Journal Article]J Trace Elem Med Biol 2017 Mar 18.JTSundararajan B, Ranjitha Kumari BD The Aedes aegypti L. mosquito transmits dengue and yellow fever, which cause millions of death every year. Dengue is a mosquito-borne viral disease that has rapidly spread worldwide particularly in cou...Publisher Full TextThe Aedes aegypti L. mosquito transmits dengue and yellow fever, which cause millions of death every year. Dengue is a mosquito-borne viral disease that has rapidly spread worldwide particularly in countries with tropical and subtropical climates areas. The present study denotes a simple and eco-friendly biosynthesis of gold nanoparticles using Artemisia vulgaris L. leaf extract as reducing agent. The synthesized gold nanoparticles were characterized by UV-Visible Spectroscopy, X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FT-IR), Dynamic Light Scattering (DLS), Zeta Potential (ZP), Transmission Electron Microscopy (TEM) and Energy Dispersive X-ray Spectroscopy (EDX). Solid state (13)C NMR was utilized to confirm the presence of larvicidal compound Beta caryophyllene in the synthesized AuNPs. Larvicidal activity of the synthesized AuNPs was measured against A. aegypti over 12 and 24h exposure periods and compared with essential oil in various concentrations (25ppm, 50ppm, 100ppm, 200ppm and 400ppm). After a 12h exposure period, the larvicidal activity of 3(rd) instar larva by AuNPs showed LC50=156.55ppm and LC90=2506.21ppm, while and essential oil displayed LC50=128.99ppm and LC90=1477.08ppm. Larvicidal activity of 4(th) instar larva by AuNPs showed LC50=97.90ppm and LC90=1677.36ppm, while essential oil displayed LC50=136.15ppm and LC90=2223.55ppm. After a 24h of exposure period, larvicidal activity of 3(rd) instar larva by AuNPs showed LC50=62.47ppm and LC90=430.16ppm and essential oil showed LC50=111.15ppm and LC90=1441.51ppm. The larvicidal activity of 4(th) instar larva and AuNPs displayed LC50=43.01ppm and LC90=376.70ppm and for essential oil LC50=74.42ppm, LC90=858.36ppm. Histopathology of A. aegypti with AuNPs for 3(rd)and 4(th) stage larvae after 24h exposure at the highest mortality concentration (400ppm) showed that the area of the midgut, epithelial cells and cortex were highly affected. The present findings demonstrate that the biosynthesis of AuNPs using A. vulgaris leaf extracts could be an eco-friendly, safer nanobiopesticide and treatment against A. aegypti which could be used to combat of dengue fever.

  • Modelling original antigenic sin in dengue viral infection.
    Modelling original antigenic sin in dengue viral infection. [Journal Article]Math Med Biol 2017 Feb 27.MMNikin-Beers R, Ciupe SM Cross-reactive T cell responses induced by a primary dengue virus infection may contribute to increased disease severity following heterologous infections with a different virus serotype in a phenomeno...Publisher Full TextCross-reactive T cell responses induced by a primary dengue virus infection may contribute to increased disease severity following heterologous infections with a different virus serotype in a phenomenon known as the original antigenic sin. In this study, we developed and analyzed in-host models of T cell responses to primary and secondary dengue virus infections that considered the effect of T cell cross-reactivity in disease enhancement. We fitted the models to published patient data and showed that the overall infected cell killing is similar in dengue heterologous infections, resulting in dengue fever and dengue hemorrhagic fever. The contribution to overall killing, however, is dominated by non-specific T cell responses during the majority of secondary dengue hemorrhagic fever cases. By contrast, more than half of secondary dengue fever cases have predominant strain-specific T cell responses with high avidity. These results support the hypothesis that cross-reactive T cell responses occur mainly during severe disease cases of heterologous dengue virus infections.

  • Human Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P) regulates cytoplasmic lipid droplet abundance: A potential target for indirect-acting anti-dengue virus agents.
    Human Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P) regulates cytoplasmic lipid droplet abundance: A potential target for indirect-acting anti-dengue virus agents. [Journal Article]PLoS One 2017; 12(3):e0174483.PlosHyrina A, Meng F, McArthur SJ, et al. Viral hijacking and manipulation of host-cell biosynthetic pathways by human enveloped viruses are shared molecular events essential for the viral lifecycle. For Flaviviridae members such as hepatitis ...Publisher Full TextViral hijacking and manipulation of host-cell biosynthetic pathways by human enveloped viruses are shared molecular events essential for the viral lifecycle. For Flaviviridae members such as hepatitis C virus and dengue virus (DENV), one of the key subsets of cellular pathways that undergo manipulation is the lipid metabolic pathways, underlining the importance of cellular lipids and, in particular, lipid droplets (LDs) in viral infection. Here, we hypothesize that targeting cellular enzymes that act as key regulators of lipid homeostasis and LD formation could represent a powerful approach to developing a novel class of broad-spectrum antivirals against infection associated with all DENV serotypes (1-4) circulating around the world. Using PF-429242, an active-site-directed inhibitor of SKI-1/S1P, we demonstrate that inhibition of SKI-1/S1P enzymatic activity in human hepatoma Huh-7.5.1 cells results in a robust reduction of the LD numbers and LD-positive areas and provides a means of effectively inhibiting infection by DENV (1-4). Pre-treatment of Huh-7.5.1 cells with PF-429242 results in a dose-dependent inhibition of DENV infection [median inhibitory dose (EC50) = 1.2 microM; median cytotoxic dose (CC50) = 81 microM; selectivity index (SI) = 68)] and a ~3-log decrease in DENV-2 titer with 20 microM of PF-429242. Post-treatment of DENV-2 infected Huh-7.5.1 cells with PF-429242 does not affect viral RNA abundance, but it does compromise the assembly and/or release of infectious virus particles. PF-429242 antiviral activity is reversed by exogenous oleic acid, which acts as an inducer of LD formation in PF-429242-treated and non-treated control cells. Collectively, our results demonstrate that human SKI-1/S1P is a potential target for indirect-acting pan-serotypic anti-DENV agents and reveal new therapeutic opportunities associated with the use of lipid-modulating drugs for controlling DENV infection.