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Viruses Sep 2023Every year, dengue virus (DENV) affects millions of people. Currently, there are no approved drugs for the treatment of DENV infection. Autophagy is a conserved...
Every year, dengue virus (DENV) affects millions of people. Currently, there are no approved drugs for the treatment of DENV infection. Autophagy is a conserved degradation process that was shown to be induced by DENV infection and required for optimal DENV replication. The modulation of autophagy is, therefore, considered an attractive target to treat DENV infection. This study carried out a high-content image screen analysis using Crispr-Cas9 GFP-LC3 knocked-in HeLa cells of a compound library synthesized from or inspired by natural products and their biocongener precursors to discover novel autophagy inhibitors. The screen identified Ka-003 as the most effective compound for decreasing the number of autophagic vacuoles inside cells upon autophagy induction. Ka-003 could inhibit autophagy in a dose-dependent manner at low micromolar concentrations. More importantly, Ka-003 demonstrated the concentration-dependent inhibition of DENV production in Crispr-Cas9 GFP-LC3 knocked-in THP-1 monocytes. The core structure of Ka-003, which is a methyl cyclohexene derivative, resembles those found in mulberry plants, and could be synthetically prepared in a bioinspired fashion. Taken together, data indicate that Ka-003 hampered autophagy and limited DENV replication. The low cytotoxicity of Ka-003 suggests its therapeutic potential, which warrants further studies for the lead optimization of the compound for dengue treatment.
Topics: Humans; Dengue Virus; HeLa Cells; Autophagy; Dengue; Virus Replication
PubMed: 37896789
DOI: 10.3390/v15102012 -
Vector Borne and Zoonotic Diseases... Oct 2019Natural infection of dengue virus (DENV) in bats is an unexplored field in Colombia. To detect the presence of DENV in bats, a descriptive prospective study using a...
Natural infection of dengue virus (DENV) in bats is an unexplored field in Colombia. To detect the presence of DENV in bats, a descriptive prospective study using a nonprobabilistic sampling was carried out; 286 bats in 12 sites were caught. Sample tissues of different animals were obtained; the RNA was obtained from tissues and a nested-RT-PCR was carried out and detected amplicons of 143 fragment of the NS5 gene were sequenced by the Sanger method. In nonhematophagous bats and captured in Ayapel and San Carlos (Córdoba), respectively, an amplicon corresponding to NS5 was detected. The amplicons showed a high similarity with serotype-2 dengue virus (DENV-2). This is the first evidence of the DENV-2 genome in bats in from the Colombian Caribbean.
Topics: Animals; Chiroptera; Colombia; DNA, Viral; Dengue; Dengue Virus; Disease Reservoirs; Polymerase Chain Reaction; Prospective Studies
PubMed: 31211661
DOI: 10.1089/vbz.2018.2324 -
Journal of Virological Methods Sep 2016We report optimized workflows for full-genome sequencing of dengue viruses (DENVs) 1-4. Based on alignments of publicly available complete genomes we modified and...
We report optimized workflows for full-genome sequencing of dengue viruses (DENVs) 1-4. Based on alignments of publicly available complete genomes we modified and expanded existing primers sets to amplify DENV genotypes that were previously difficult or impossible to sequence. We also report improvements to streamline laboratory handling, including a dual amplification strategy for easy and difficult to sequence "high-copy" and "low-copy" templates, respectively, and normalization of PCR cycling conditions across serotypes. High-copy templates can be sequenced following amplification of as few as 5 overlapping segments covering the complete viral genome, whereas low-copy templates can be sequenced following amplification of no more than 10 overlapping segments of smaller size. These changes have been validated using a balanced set of wild-type DENV genomes (11 of DENV1, 14 of DENV2, 13 of DENV3 and 7 of DENV4) derived from human serum samples collected throughout South America over the past 15 years. The changes described enable generation of complete DENV genomes from wild-type samples without the need for viral enrichment via passaging through laboratory cell lines. This should facilitate quick and cost-effective generation of DENV full-genome sequences of the type needed for accurate epidemiological surveillance and thorough evolutionary studies of wild-type DENVs.
Topics: DNA Primers; Dengue; Dengue Virus; Evolution, Molecular; Genome, Viral; Genotype; High-Throughput Nucleotide Sequencing; Humans; Polymerase Chain Reaction; RNA, Viral; Sequence Analysis, DNA
PubMed: 27334982
DOI: 10.1016/j.jviromet.2016.06.001 -
Current Opinion in Virology Oct 2016If a freshly minted genome contains a mutation that confers drug resistance, will it be selected in the presence of the drug? Not necessarily. During viral infections,... (Review)
Review
If a freshly minted genome contains a mutation that confers drug resistance, will it be selected in the presence of the drug? Not necessarily. During viral infections, newly synthesized viral genomes occupy the same cells as parent and other progeny genomes. If the antiviral target is chosen so that the drug-resistant progeny's growth is dominantly inhibited by the drug-susceptible members of its intracellular family, its outgrowth can be suppressed. Precedent for 'dominant drug targeting' as a deliberate approach to suppress the outgrowth of inhibitor-resistant viruses has been established for envelope variants of vesicular stomatitis virus and for capsid variants of poliovirus and dengue virus. Small molecules that stabilize oligomeric assemblages are a promising means to an unfit family to destroy the effectiveness of a newborn drug-resistant relative due to the co-assembly of drug-susceptible and drug-resistant monomers.
Topics: Antiviral Agents; Dengue Virus; Drug Resistance, Viral; Genetics, Population; Humans; Poliovirus; Selection, Genetic; Vesiculovirus; Virus Replication
PubMed: 27764731
DOI: 10.1016/j.coviro.2016.09.011 -
Journal of Infection in Developing... Apr 2024After the Coronavirus Disease 2019 pandemic, a high number of cases and severe dengue in children were reported in some provinces in the south of Vietnam. This study...
INTRODUCTION
After the Coronavirus Disease 2019 pandemic, a high number of cases and severe dengue in children were reported in some provinces in the south of Vietnam. This study aimed to determine the distribution of dengue virus serotypes and their correlation with demographic factors, disease severity, clinical manifestations, and laboratory findings.
METHODOLOGY
This study employed a cross-sectional design. Ninety-six dengue-infected children admitted to Can Tho Children's Hospital between October 2022 and March 2023 were included. Confirmation of dengue infection was achieved through the real-time polymerase chain reaction (RT-PCR).
RESULTS
Among the identified serotypes, DENV-2 accounted for the highest proportion (71.87%), followed by DENV-1 (23.96%), and DENV-4 (4.17%). DENV-3 was not detected. No significant demographic, disease severity, or laboratory differences were observed among the identified dengue serotypes. However, DENV-2 was associated with a higher occurrence of mucous membrane hemorrhages and gastrointestinal bleeding compared to other serotypes.
CONCLUSIONS
Although DENV-2 was the most prevalent serotype responsible for dengue in children in southern Vietnam, it did not lead to more severe cases compared to other serotypes. This finding is crucial for evaluating the illness's prognosis.
Topics: Humans; Vietnam; Severe Dengue; Cross-Sectional Studies; Male; Dengue Virus; Female; Serogroup; Child; Child, Preschool; Adolescent; Infant; Severity of Illness Index
PubMed: 38728633
DOI: 10.3855/jidc.18900 -
Current Opinion in Virology Aug 2014The endothelial lining of the vasculature performs a vital role in maintaining fluid barrier functions despite balancing nutrient and fluid content of tissues, repairing... (Review)
Review
The endothelial lining of the vasculature performs a vital role in maintaining fluid barrier functions despite balancing nutrient and fluid content of tissues, repairing localized damage, coordinating responses of a plethora of factors, immune cells and platelets through a multitude of endothelial cell surface receptors. Viruses that nonlytically cause lethal hemorrhagic or edematous diseases engage receptors on vascular and lymphatic endothelial cells, altering normal cellular responses that control capillary leakage and fluid clearance functions with lethal consequences. Recent studies indicate that receptors directing dengue virus and hantavirus infection of the endothelium contribute to the dysregulation of normal endothelial cell signaling responses that control capillary permeability and immune responses that contribute to pathogenesis. Here we present recent studies of virally altered endothelial functions that provide new insight into targeting barrier functions of the endothelium as a potential therapeutic approach.
Topics: Animals; Dengue; Dengue Virus; Endothelial Cells; Orthohantavirus; Hantavirus Infections; Humans; Receptors, Virus
PubMed: 25063986
DOI: 10.1016/j.coviro.2014.06.006 -
Current Opinion in Virology Aug 2020Despite the high disease burden of dengue virus, there is no approved antiviral treatment or broadly applicable vaccine to treat or prevent dengue virus infection. In... (Review)
Review
Despite the high disease burden of dengue virus, there is no approved antiviral treatment or broadly applicable vaccine to treat or prevent dengue virus infection. In the last decade, many antiviral compounds have been identified but only few have been further evaluated in pre-clinical or clinical trials. This review will give an overview of the direct-acting and host-directed antivirals identified to date. Furthermore, important parameters for further development that is, drug properties including efficacy, specificity and stability, pre-clinical animal testing, and combinational drug therapy will be discussed.
Topics: Animals; Antiviral Agents; Dengue; Dengue Virus; Drug Development; Humans
PubMed: 32795907
DOI: 10.1016/j.coviro.2020.07.009 -
Biomolecules Dec 2020Phenolic compounds have been related to multiple biological activities, and the antiviral effect of these compounds has been demonstrated in several viral models of... (Review)
Review
Phenolic compounds have been related to multiple biological activities, and the antiviral effect of these compounds has been demonstrated in several viral models of public health concern. In this review, we show the antiviral role of phenolic compounds against dengue virus (DENV), the most widespread arbovirus globally that, after its re-emergence, has caused multiple epidemic outbreaks, especially in the last two years. Twenty phenolic compounds with anti-DENV activity are discussed, including the multiple mechanisms of action, such as those directed against viral particles or viral proteins, host proteins or pathways related to the productive replication viral cycle and the spread of the infection.
Topics: Animals; Antiviral Agents; Chlorocebus aethiops; Dengue; Dengue Virus; Humans; Phenols; Plant Extracts; Vero Cells; Viral Proteins; Virus Replication
PubMed: 33374457
DOI: 10.3390/biom11010011 -
Virology Mar 2023Dengue infections pose a critical threat to public health worldwide. Since there are no clinically approved antiviral drugs to treat dengue infections caused by the four...
Dengue infections pose a critical threat to public health worldwide. Since there are no clinically approved antiviral drugs to treat dengue infections caused by the four dengue virus (DENV) serotypes, there is an urgent need to develop effective antivirals. Peptides are promising antiviral candidates due to their specificity and non-toxic properties. The DENV envelope (E) protein was selected for the design of antiviral peptides due to its importance in receptor binding and viral fusion to the host cell membrane. Twelve novel peptides were designed to mimic regions containing critical amino acid residues of the DENV E protein required for interaction with the host. A total of four peptides were identified to exhibit potent inhibitory effects against at least three or all four DENV serotypes. Peptide 3 demonstrated all three modes of action: cell protection and inhibition of post-infection against all four DENV serotypes, whereas direct virus-inactivating effects were only observed against DENV-2, 3, and 4. Peptide 4 showed good direct virus-inactivating effects against DENV-2 (74.26%) as well as good inhibitions of DENV-1 (80.37%) and DENV-4 (72.22%) during the post-infection stage. Peptide 5 exhibited direct virus-inactivating effects against all four DENV serotypes, albeit at lower inhibition levels against DENV-1 and DENV-3. It also exhibited highly significant inhibition of DENV-4 (89.31%) during post-infection. Truncated peptide 5F which was derived from peptide 5 showed more significant inhibition of DENV-4 (91.58%) during post-infection and good direct virus-inactivating effects against DENV-2 (77.55%) at a lower concentration of 100 μM. Peptide 3 could be considered as the best antiviral candidate for pre- and post-infection treatments of DENV infections in regions with four circulating dengue serotypes. However, if the most predominant dengue serotype for a particular region could be identified, peptides with significantly high antiviral activities against that particular dengue serotype could serve as more suitable antiviral candidates. Thus, peptide 5F serves as a more suitable antiviral candidate for post-infection treatment against DENV-4.
Topics: Humans; Dengue Virus; Dengue; Serogroup; Antiviral Agents; Peptides
PubMed: 36739680
DOI: 10.1016/j.virol.2023.01.016 -
PLoS Neglected Tropical Diseases May 2017A high number of dengue cases are reported annually in Bali. Despite the endemicity, limited data on dengue is available for Bali localities. Molecular surveillance...
A high number of dengue cases are reported annually in Bali. Despite the endemicity, limited data on dengue is available for Bali localities. Molecular surveillance study was conducted to explore the clinical and virological characteristics of dengue patients in urban Denpasar and rural Gianyar areas in Bali during the peak season in 2015. A total of 205 adult dengue-suspected patients were recruited in a prospective cross-sectional study. Demographic and clinical information were obtained, and dengue screening was performed using NS1 and IgM/IgG ELISAs. Viral RNA was subsequently extracted from patients' sera for serotyping using conventional RT-PCR and Simplexa Dengue real-time RT-PCR, followed by genotyping with sequencing method. We confirmed 161 patients as having dengue by NS1 and RT-PCR. Among 154 samples successfully serotyped, the DENV-3 was predominant, followed by DENV-1, DENV-2, and DENV-4. Serotype predominance was different between Denpasar and Gianyar. Genotyping results classify DENV-1 isolates into Genotype I and DENV-2 as Cosmopolitan Genotype. The classification grouped isolates into Genotype I and II for DENV-3 and DENV-4, respectively. Clinical parameters showed no relationship between infecting serotypes and severity. We observed the genetic diversity of circulating DENV isolates and their relatedness with historical data and importation to other countries. Our data highlights the role of this tourist destination as a potential source of dengue transmission in the region.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Viral; Cross-Sectional Studies; Dengue; Dengue Virus; Enzyme-Linked Immunosorbent Assay; Female; Genetic Variation; Genotyping Techniques; Humans; Indonesia; Male; Middle Aged; Prospective Studies; RNA, Viral; Reverse Transcriptase Polymerase Chain Reaction; Sequence Analysis, DNA; Serogroup; Young Adult
PubMed: 28531223
DOI: 10.1371/journal.pntd.0005483