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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.


  • Discovery of selective dengue virus inhibitors using combination of molecular fingerprint-based virtual screening protocols, structure-based pharmacophore model development, molecular dynamics simulations and in vitro studies.
    Discovery of selective dengue virus inhibitors using combination of molecular fingerprint-based virtual screening protocols, structure-based pharmacophore model development, molecular dynamics simulations and in vitro studies. [Journal Article]J Mol Graph Model 2017 Oct 24.:88-102.JMMirza SB, Lee RCH, Chu JJH, et al. Dengue virus is a major issue of tropical and sub-tropical regions. The proliferation of virus results in immense number of deaths each year because of unavailability of on-shelf drugs. This issue nece...Publisher Full TextDengue virus is a major issue of tropical and sub-tropical regions. The proliferation of virus results in immense number of deaths each year because of unavailability of on-shelf drugs. This issue necessitates the design of novel anti-Dengue drugs. The protease enzyme pathway is the critical target for drug design due to its significance in the replication, survival and other cellular activities of Dengue virus. Keeping in mind the worsening situation regarding Dengue virus, approximately eighteen million drug-like compounds from the ZINC small molecule database have been screened against Nonstructural Protein 3 (NS3) previously by our group. In this study, in order to investigate the effect of extended time of molecular dynamics (MD) simulations on structural and dynamical profiles of used complexes, simulation run time is increased from 50-ns to 100-ns for the each system. In addition, a well-known Dengue virus inhibitor (MB21) from literature is used as reference structure (positive control) to compare the proposed molecules. Post-processing MD analyses including Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) calculations were conducted to predict binding free energies of inhibitors from derived trajectory frames of MD simulations. Identified compounds are further directed to Quantum-Polarized Ligand Docking (QPLD), molecular fingerprint-based virtual screening of another small molecule database (Otava Drug Like small molecule database), and Structure-based Pharmacophore Modeling (E-Pharmacophore). Finally, cell proliferation and cytotoxicity tests as well as pre- and post-treatment on HUH7 cells infected with DENV2 NGC strain are applied for four identified hit molecules (ZINC36681949, ZINC44921800, ZINC95518765 and ZINC39500661) to check whether these drugs inhibit DENV2 from entry and/or exit pathways. Based on cell-based Dengue quantification assays, there is no effect seen on pre-treatment of cells with these compounds indicating that the early infection processes of virus is not affected. In contrast, the post-treatment of cells with these compounds after Dengue virus infection has resulted in a significant 1 log PFU/ml reduction of the virus infectious titre.

  • Robust real-time cell analysis method for determining viral infectious titers during development of a viral vaccine production process.
    Robust real-time cell analysis method for determining viral infectious titers during development of a viral vaccine production process. [Journal Article]J Virol Methods 2017 Nov 14.JVCharretier C, Saulnier A, Benair L, et al. The classical cell-culture methods, such as cell culture infectious dose 50% (CCID50) assays, are time-consuming, end-point assays currently used during the development of a viral vaccine production pr...Publisher Full TextThe classical cell-culture methods, such as cell culture infectious dose 50% (CCID50) assays, are time-consuming, end-point assays currently used during the development of a viral vaccine production process to measure viral infectious titers. However, they are not suitable for handling the large number of tests required for high-throughput and large-scale screening analyses. Impedance-based bio-sensing techniques used in real-time cell analysis (RTCA) to assess cell layer biological status in vitro, provide real-time data. In this proof-of-concept study, we assessed the correlation between the results from CCID50 and RTCA assays and compared time and costs using monovalent and tetravalent chimeric yellow fever dengue (CYD) vaccine strains. For the RTCA assay, Vero cells were infected with the CYD sample and real-time impedance was recorded, using the dimensionless cell index (CI). The CI peaked just after infection and decreased as the viral cytopathic effect occurred in a dose-dependent manner. The time to the median CI (CITmed) was correlated with viral titers determined by CCID50 over a range of about 4-5log10 CCID50/ml. This in-house RTCA virus-titration assay was shown to be a robust method for determining real-time viral infectious titers, and could be an alternative to the classical CCID50 assay during the development of viral vaccine production process.

  • The antimicrobial peptide HS-1 inhibits dengue virus infection.
    The antimicrobial peptide HS-1 inhibits dengue virus infection. [Journal Article]Virology 2017 Nov 16.:79-87.VMonteiro JMC, Oliveira MD, Dias RS, et al. Dengue virus (DENV) is an arbovirus that belongs to the Flaviviridae family. Studies reveal that peptides secreted by amphibians have many functions, such as antiviral and antimicrobial activities. As ...Publisher Full TextDengue virus (DENV) is an arbovirus that belongs to the Flaviviridae family. Studies reveal that peptides secreted by amphibians have many functions, such as antiviral and antimicrobial activities. As there is no antiviral drug effective against the DENV, the antiviral activity of a synthetic peptide called HS-1, derived from the secretion of the anuran Hypsiboas semilineatus, has been evaluated. The assays of neutralization in the Vero cells show a complete inhibition of infection of the serotypes 2 and 3. Furthermore, the direct action of peptides on the viral particle can be observed through atomic force microscopy. In vivo tests display 80% protection against the dengue-2 virus due to the presence of HS-1, which reveals its potential as an antiviral against the DENV.

  • Generation and characterization of cross neutralizing human monoclonal antibody against 4 serotypes of dengue virus without enhancing activity.
    Generation and characterization of cross neutralizing human monoclonal antibody against 4 serotypes of dengue virus without enhancing activity. [Journal Article]PeerJ 2017.:e4021.PInjampa S, Muenngern N, Pipattanaboon C, et al. Dengue disease is a leading cause of illness and death in the tropics and subtropics. Most severe cases occur among patients secondarily infected with a different dengue virus (DENV) serotype compared ...Dengue disease is a leading cause of illness and death in the tropics and subtropics. Most severe cases occur among patients secondarily infected with a different dengue virus (DENV) serotype compared with that from the first infection, resulting in antibody-dependent enhancement activity (ADE). Our previous study generated the neutralizing human monoclonal antibody, D23-1B3B9 (B3B9), targeting the first domain II of E protein, which showed strong neutralizing activity (NT) against all four DENV serotypes. However, at sub-neutralizing concentrations, it showed ADE activity in vitro.In this study, we constructed a new expression plasmid using the existing IgG heavy chain plasmid as a template for Fc modification at position N297Q by site-directed mutagenesis. The resulting plasmid was then co-transfected with a light chain plasmid to produce full recombinant IgG (rIgG) in mammalian cells (N297Q-B3B9). This rIgG was characterized for neutralizing and enhancing activity by using different FcγR bearing cells. To produce sufficient quantities of B3B9 rIgG for further characterization, CHO-K1 cells stably secreting N297Q-B3B9 rIgG were then established.The generated N297Q-B3B9 rIgG which targets the conserved N-terminal fusion loop of DENV envelope protein showed the same cross-neutralizing activity to all four DENV serotypes as those of wild type rIgG. In both FcγRI- and RII-bearing THP-1 cells and FcγRII-bearing K562 cells, N297Q-B3B9 rIgG lacked ADE activity against all DENV serotypes at sub-neutralizing concentrations. Fortunately, the N297Q-B3B9 rIgG secreted from stable cells showed the same patterns of NT and ADE activities as those of the N297Q-B3B9 rIgG obtained from transient expression against DENV2. Thus, the CHO-K1 stably expressing N297Q-B3B9 HuMAb can be developed as high producer stable cells and used to produce sufficient amounts of antibody for further characterization as a promising dengue therapeutic candidate.Human monoclonal antibody, targeted to fusion loop of envelope domainII (EDII), was generated and showed cross-neutralizing activity to 4 serotypes of DENV, but did not cause any viral enhancement activity in vitro. This HuMAb could be further developed as therapeutic candidates.

  • Effective population sizes of a major vector of human diseases, Aedes aegypti.
    Effective population sizes of a major vector of human diseases, Aedes aegypti. [Journal Article]Evol Appl 2017 Dec; 10(10):1031-1039.EASaarman NP, Gloria-Soria A, Anderson EC, et al. The effective population size (Ne ) is a fundamental parameter in population genetics that determines the relative strength of selection and random genetic drift, the effect of migration, levels of inb...The effective population size (Ne ) is a fundamental parameter in population genetics that determines the relative strength of selection and random genetic drift, the effect of migration, levels of inbreeding, and linkage disequilibrium. In many cases where it has been estimated in animals, Ne is on the order of 10%-20% of the census size. In this study, we use 12 microsatellite markers and 14,888 single nucleotide polymorphisms (SNPs) to empirically estimate Ne in Aedes aegypti, the major vector of yellow fever, dengue, chikungunya, and Zika viruses. We used the method of temporal sampling to estimate Ne on a global dataset made up of 46 samples of Ae. aegypti that included multiple time points from 17 widely distributed geographic localities. Our Ne estimates for Ae. aegypti fell within a broad range (~25-3,000) and averaged between 400 and 600 across all localities and time points sampled. Adult census size (Nc) estimates for this species range between one and five thousand, so the Ne /Nc ratio is about the same as for most animals. These Ne values are lower than estimates available for other insects and have important implications for the design of genetic control strategies to reduce the impact of this species of mosquito on human health.

  • Chikungunya Infection in Solid Organ Transplant Recipients.
    Chikungunya Infection in Solid Organ Transplant Recipients. [Journal Article]Transplant Proc 2017 Nov; 49(9):2076-2081.TPGirão ES, Rodrigues Dos Santos BG, do Amaral ES, et al. SOT with CHIKV infection seems to have a clinical presentation and evolution similar to those seen in the general population, with no apparent damage to the graft.Aggregator Full TextChikungunya virus (CHIKV) is an emerging mosquito-borne disease that causes acute febrile polyarthralgia and arthritis. CHIKV has spread rapidly to the Americas and, in Brazil, autochthonous cases are increasingly been reported. Solid organ transplant (SOT) recipients who travel to or live in CHIKV endemic areas are under high risk of acquiring the disease. Few data exist regarding the clinical characteristics of CHIKV infections in this population. We report the first case series of CHIKV infection in SOT recipients.We retrospectively evaluated 13 cases of CHIKV infection in SOT recipients between January 2016 and December 2016 confirmed by laboratory tests and transplanted in the Renal and Liver Transplant Units of Walter Cantídio University Hospital from Federal University of Ceará.Positive CHIKV serology (enzyme-linked immunosorbent assay immunoglobulin M) was found in all patients (9 kidney and 4 liver transplant recipients). All of these patients had been living in endemic areas for dengue and CHIKV in the past months before the illness. The mean time between transplantation and CHIKV infection was of 7.2 years. Fever presented in 11 (84.6%) patients and 5 (38.5%) presented with a maculopapular rash. All cases had joint symptoms: 11 (84.6%) with symmetrical and peripheral polyarthralgia/polyarthritis and 2 (15.3%) with monoarthralgia/monoarthritis. Six (46%) patients had a joint complaint that lasted 3 months. Two patients had concomitant positive dengue serology (enzyme-linked immunosorbent assay immunoglobulin M). There were no cases of complications or deaths.SOT with CHIKV infection seems to have a clinical presentation and evolution similar to those seen in the general population, with no apparent damage to the graft.

  • Vector-borne diseases and climate change: a European perspective.
    Vector-borne diseases and climate change: a European perspective. [Journal Article]FEMS Microbiol Lett 2017 Nov 15.FMSemenza JC, Suk JE Climate change has already impacted the transmission of a wide-range of vector-borne diseases in Europe, and it will continue to do so in the coming decades. Climate change has been implicated in the o...Publisher Full TextPublisher Full TextClimate change has already impacted the transmission of a wide-range of vector-borne diseases in Europe, and it will continue to do so in the coming decades. Climate change has been implicated in the observed shift of ticks to elevated altitudes and latitudes, notably including the Ixodes ricinus tick species which is a vector for Lyme borreliosis and tick-borne encephalitis. Climate change is also thought to have been a factor in the expansion of other important disease vectors in Europe: Aedes albopictus (the Asian tiger mosquito), which transmits diseases such as Zika, dengue, and chikungunya, and Phlebotomus sandfly species, which transmits diseases including Leishmaniasis. In addition, highly elevated temperatures in the summer of 2010 have been associated with an epidemic of West Nile Fever in Southeast Europe and subsequent outbreaks have been linked to summer temperature anomalies.Future climate-sensitive health impacts are challenging to project quantitatively, in part due to the intricate interplay between non-climatic and climatic drivers, weather-sensitive pathogens, and climate change adaptation. Moreover, globalisation and international air travel contribute to pathogen and vector dispersion internationally. Nevertheless, monitoring forecasts of meteorological conditions can help detect epidemic precursors of vector-borne disease outbreaks and serve as early warning systems for risk reduction.

  • The introduction of dengue follows transportation infrastructure changes in the state of Acre, Brazil: A network-based analysis.
    The introduction of dengue follows transportation infrastructure changes in the state of Acre, Brazil: A network-based analysis. [Journal Article]PLoS Negl Trop Dis 2017 Nov; 11(11):e0006070.PNLana RM, Gomes MFDC, Lima TFM, et al. Human mobility, presence and passive transportation of Aedes aegypti mosquito, and environmental characteristics are a group of factors which contribute to the success of dengue spread and establishmen...Publisher Full TextHuman mobility, presence and passive transportation of Aedes aegypti mosquito, and environmental characteristics are a group of factors which contribute to the success of dengue spread and establishment. To understand this process, we assess data from dengue national and municipal basins regarding population and demographics, transportation network, human mobility, and Ae. aegypti monitoring for the Brazilian state of Acre since the first recorded dengue case in the year 2000 to the year 2015. During this period, several changes in Acre's transport infrastructure and urbanization have been started. To reconstruct the process of dengue introduction in Acre, we propose an analytic framework based on concepts used in malaria literature, namely vulnerability and receptivity, to inform risk assessments in dengue-free regions as well as network theory concepts for disease invasion and propagation. We calculate the probability of dengue importation to Acre from other Brazilian states, the evolution of dengue spread between Acrean municipalities and dengue establishment in the state. Our findings suggest that the landscape changes associated with human mobility have created favorable conditions for the establishment of dengue virus transmission in Acre. The revitalization of its major roads, as well as the increased accessibility by air to and within the state, have increased dengue vulnerability. Unplanned urbanization and population growth, as observed in Acre during the period of study, contribute to ideal conditions for Ae. aegypti mosquito establishment, increase the difficulty in mosquito control and consequently its local receptivity.

  • Diagnostic Accuracy of Parameters for Zika and Dengue Virus Infections, Singapore.
    Diagnostic Accuracy of Parameters for Zika and Dengue Virus Infections, Singapore. [Journal Article]Emerg Infect Dis 2017 Dec; 23(12):2085-2088.EIHo HJ, Wong JGX, Mar Kyaw W, et al. Singapore experienced its first documented Zika virus outbreak in 2016. We identified clinical and laboratory parameters that increase the probability for Zika or dengue virus infection. Early during t...Singapore experienced its first documented Zika virus outbreak in 2016. We identified clinical and laboratory parameters that increase the probability for Zika or dengue virus infection. Early during the illness, combinations of key parameters obtained through clinical assessment and hematologic tests can help distinguish between these infections.

  • Pharmacophoric characteristics of dengue virus NS2B/NS3pro inhibitors: a systematic review of the most promising compounds.
    Pharmacophoric characteristics of dengue virus NS2B/NS3pro inhibitors: a systematic review of the most promising compounds. [Journal Article, Review]Arch Virol 2017 Nov 16.AVLeonel CA, Lima WG, Dos Santos M, et al. Dengue virus (DENV) infection can lead to a wide range of clinical manifestations, including fatal hemorrhagic complications. There is a need to find effective pharmacotherapies to treat this disease d...Publisher Full TextDengue virus (DENV) infection can lead to a wide range of clinical manifestations, including fatal hemorrhagic complications. There is a need to find effective pharmacotherapies to treat this disease due to the lack of specific immunotherapies and antiviral drugs. That said, the DENV NS2B/NS3pro protease complex is essential in both the viral multiplication cycle and in disease pathogenesis, and is considered a promising target for new antiviral therapies. Here, we performed a systematic review to evaluate the pharmacophoric characteristics of promising compounds against NS2B/NS3pro reported in the past 10 years. Online searches in the PUBMED/MEDLINE and SCOPUS databases resulted in 165 articles. Eight studies, which evaluated 3,384,268 molecules exhibiting protease inhibition activity, were included in this review. These studies evaluated anti-dengue activity in vitro and the IC50 and EC50 values were provided. Most compounds exhibited non-competitive inhibition. Cytotoxicity was evaluated in BHK-21, Vero, and LLC-MK2 cells, and the CC50 values obtained ranged from < 1.0 to 780.5 µM. Several groups were associated with biological activity against dengue, including nitro, catechol, halogen and ammonium quaternaries. Thus, these groups seem to be potential pharmacophores that can be further investigated to treat dengue infections.