1,2,4Triazolo1,5-apyrimidine derivative (Mol-5) is a new NS5-RdRp inhibitor of DENV2 proliferation and DENV2-induced inflammation.

[1,2,4]Triazolo[1,5-a]pyrimidine derivative (Mol-5) is a new NS5-RdRp inhibitor of DENV2 proliferation and DENV2-induced inflammation. Acta Pharmacol Sin. 2019 Nov 15;: Authors: Wan YH, Wu WY, Guo SX, He SJ, Tang XD, Wu XY, Nandakumar KS, Zou M, Li L, Chen XG, Liu SW, Yao XG Abstract Dengue fever is an acute infectious disease caused by dengue virus (DENV) and transmitted by Aedes mosquitoes. There is no effective vaccine or antiviral drug available to date to prevent or treat dengue disease. Recently, RNA-dependent RNA polymerase (RdRp), a class of polymerases involved in the synthesis of complementary RNA strands using single-stranded RNA, has been proposed as a promising drug target. Hence, we screened new molecules against DENV RdRp using our previously constructed virtual screening method. Mol-5, [1,2,4]triazolo[1,5-a]pyrimidine derivative, was screened out from an antiviral compound library (~8000 molecules). Using biophysical methods, we confirmed the direct interactions between mol-5 and purified DENV RdRp protein. In luciferase assay, mol-5 inhibited NS5-RdRp activity with an IC50 value of 1.28 ± 0.2 μM. In the cell-based cytopathic effect (CPE) assay, mol-5 inhibited DENV2 infectivity with an EC50 value of 4.5 ± 0.08 μM. Mol-5 also potently inhibited DENV2 RNA replication as observed in immunofluorescence assay and qRT-PCR. Both the viral structural (E) and non-structural (NS1) prote...
Source: Acta Pharmacologica Sinica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharmacol Sin Source Type: research

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Abstract Dengue is one of the most serious mosquito-borne viral diseases occurring in humans. From their complexity of 4 serotypes, the ideal vaccine for dengue should be able to stimulate cross-neutralizing antibodies. Recently, genetic-based immune response have been studied for guiding of vaccine design for several viral pathogens. Despite a recent approval of dengue vaccine, the information of genetics-based immune response against dengue virus (DENV) are still limited. Consequently, we aimed to determine the profiles of immunoglobulin heavy chain gene from DENV2 infected patients. The immunoglobulin heavy cha...
Source: Japanese Journal of Infectious Diseases - Category: Infectious Diseases Authors: Tags: Jpn J Infect Dis Source Type: research
Source: ScienceNOW - Category: Science Authors: Tags: letters Source Type: news
(Cornell University) In a new paper in Science Signaling, researchers at the University of Hyderabad in India and the Cornell University College of Veterinary Medicine show that a plant-based compound called halofuginone improves the immune response to a potential vaccine against dengue virus.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
Conclusion: The study highlights the importance of behavioral change for knowledge and attitude to have significant effect to practices against DF. Thus, we recommend two comprehensive health programs, Communication for Behavioral Impact (COMBI) and Health Belief Model (HBM).
Source: International Journal of Environmental Research and Public Health - Category: Environmental Health Authors: Tags: Article Source Type: research
An additional six months of data from a late-stage trial of Takeda Pharmaceutical Co's experimental dengue vaccine again showed it failed to protect against one of the four types of the virus in an important patient group, researchers said on Saturday.
Source: Reuters: Health - Category: Consumer Health News Tags: healthNews Source Type: news
Publication date: Available online 21 November 2019Source: The Brazilian Journal of Infectious DiseasesAuthor(s): Gilma Sánchez-Burgos, Carla Herrera-Nájera, Roberto Cedillo-Rivera, Eric DumonteilAbstractThe antigenic potential of seven immunogenic peptides of the dengue virus was evaluated in the sera of patients with dengue confirmed by IgM/IgG serology. Antibodies IgM and IgG against dengue virus peptides were analyzed by ELISA in 31 dengue sero-positive and 20 sero-negative patients. The P5 peptide showed significant IgG immunoreactivity mostly in the sera of patients with dengue without warning signs in ...
Source: The Brazilian Journal of Infectious Diseases - Category: Infectious Diseases Source Type: research
Dumonteil E Abstract The antigenic potential of seven immunogenic peptides of the dengue virus was evaluated in the sera of patients with dengue confirmed by IgM/IgG serology. Antibodies IgM and IgG against dengue virus peptides were analyzed by ELISA in 31 dengue sero-positive and 20 sero-negative patients. The P5 peptide showed significant IgG immunoreactivity mostly in the sera of patients with dengue without warning signs in comparison with patients with dengue with warning signs, correlating with mild disease. This finding suggests that the low antibody response against P5 epitope could be a risk factor for h...
Source: Braz J Infect Dis - Category: Infectious Diseases Authors: Tags: Braz J Infect Dis Source Type: research
Understanding T  cell responses to dengue infection is important for developing effective vaccines. Chng et al. used high-dimensional CyTOF profiling and peptide-HLA tetramer screening to track dengue-specific T cell activation and differentiation into memory cells in naturally infected patients. They found that dengue infection causes broad immune cell activation and that dengue-specific T cells differentiate into two major cell fates.
Source: Immunity - Category: Allergy & Immunology Authors: Tags: Resource Source Type: research
Publication date: 16 November 2019Source: New Scientist, Volume 244, Issue 3256Author(s): Sam WongA vaccine based on a weakened version of the dengue virus was 80 per cent effective at preventing infections after one year in a trial of 20,000 children
Source: New Scientist - Category: Science Source Type: research
Lu Lu Recently, Zika virus (ZIKV) has attracted much attention in consideration of its association with severe neurological complications including fetal microcephaly. However, there are currently no prophylactic vaccines or therapeutic drugs approved for clinical treatments of ZIKV infection. To determine the potential anti-ZIKV inhibitors, we screened a library of clinical drugs with good safety profiles. Erythromycin estolate (Ery-Est), one of the macrolide antibiotics, was found to effectively inhibit ZIKV infection in different cell types and significantly protect A129 mice from ZIKV-associated neurological sign...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research
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