-
Current Opinion in Virology Aug 2020Dengue virus infects several million people each year. Although usually a self-limiting disease, some patients can develop life-threatening severe complications,... (Review)
Review
Dengue virus infects several million people each year. Although usually a self-limiting disease, some patients can develop life-threatening severe complications, characterized by plasma leakage, hemorrhaging, and shock. The signs and symptoms of severe disease usually arise late in the disease course when patients are recovering and fever has subsided, making it difficult to predict. Efforts are underway to identify risk factors and biomarkers that can accurately predict disease severity in the acute febrile phase of the disease, facilitating early intervention and treatment strategies for those at greatest risk. In this review we discuss recent advancements in identifying risk factors and biomarkers for the prognosis of severe dengue.
Topics: Animals; Biomarkers; Dengue Virus; Humans; Prognosis; Risk Factors; Severe Dengue; Severity of Illness Index
PubMed: 32688269
DOI: 10.1016/j.coviro.2020.06.008 -
Molecules (Basel, Switzerland) Feb 2021Dengue fever is one of the most common viral infections affecting humans. It is an expanding public health problem, particularly in tropical and subtropical regions. No... (Review)
Review
Dengue fever is one of the most common viral infections affecting humans. It is an expanding public health problem, particularly in tropical and subtropical regions. No effective vaccine or antiviral therapies against Dengue virus (DENV) infection are available. Therefore, there is a strong need to develop safe and effective therapeutic strategies that can reduce the burden and duration of hospitalizations due to this life-threatening disease. Oligonucleotide-based strategies are considered as an attractive means of inhibiting viral replication since oligonucleotides can be designed to interact with any viral RNA, provided its sequence is known. The resultant targeted destruction of viral RNA interferes with viral replication without inducing any adverse effects on cellular processes. In this review, we elaborate the ribozymes, RNA interference, CRISPR, aptamer and morpholino strategies for the inhibition of DENV replication and discuss the challenges involved in utilizing such approaches.
Topics: Antiviral Agents; Dengue; Dengue Virus; Humans; Oligonucleotides; RNA Interference; Virus Replication
PubMed: 33670247
DOI: 10.3390/molecules26040956 -
Animal Models and Experimental Medicine Oct 2022Dengue virus (DENV) is one of the most important arboviral pathogens in the tropics and subtropics, and nearly one-third of the world's population is at risk of... (Review)
Review
Dengue virus (DENV) is one of the most important arboviral pathogens in the tropics and subtropics, and nearly one-third of the world's population is at risk of infection. The transmission of DENV involves a sylvatic cycle between nonhuman primates (NHP) and Aedes genus mosquitoes, and an endemic cycle between human hosts and predominantly Aedes aegypti. DENV belongs to the genus Flavivirus of the family Flaviviridae and consists of four antigenically distinct serotypes (DENV-1-4). Phylogenetic analyses of DENV have revealed its origin, epidemiology, and the drivers that determine its molecular evolution in nature. This review discusses how phylogenetic research has improved our understanding of DENV evolution and how it affects viral ecology and improved our ability to analyze and predict future DENV emergence.
Topics: Animals; Humans; Dengue Virus; Dengue; Phylogeny; Mosquito Vectors; Aedes
PubMed: 36245335
DOI: 10.1002/ame2.12283 -
Current Medicinal Chemistry 2021Dengue, the oldest and the most prevalent mosquito-borne illness, is caused by the dengue virus (DENV), from the family of Flaviviridae. It infects approximately 400... (Review)
Review
Dengue, the oldest and the most prevalent mosquito-borne illness, is caused by the dengue virus (DENV), from the family of Flaviviridae. It infects approximately 400 million individuals per annum, with approximately half of the global population residing in high-risk areas. The factors attributed to the geographic expansion of dengue, include urbanization, population density, modern means of transportation, international travels, habit modification, climate change, virus genetics, vector capacity, and poor vector control. Despite the significant progress made in the past against dengue, no effective antiviral therapy is currently available. Among the structural and non-structural proteins encoded by DENV genome, the NS2B-NS3 protease complex is amongst the extensively studied targets for the development of antiviral therapeutics owing to its multiple roles in virus life cycle. Furthermore, protease inhibitors were found to be successful in Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV). Likewise, several peptidic, peptide derived/peptidomimetic, and small molecules inhibitors have been identified as DENV protease inhibitors. Unfortunately, none of them have resulted in a clinically approved drug. Considering all the abovementioned facts, this review descriptively explains the molecular mechanism and therapeutic potential of DENV protease along with an up to date information on various competitive inhibitors reported against DENV protease. This review might be helpful for the researchers working in this area to understand the critical aspects of DENV protease that will help them develop effective and novel inhibitors against DENV to protect lives of millions of people worldwide.
Topics: Animals; Antiviral Agents; Dengue Virus; Humans; Peptide Hydrolases; Protease Inhibitors; Serine Endopeptidases; Viral Nonstructural Proteins
PubMed: 34212826
DOI: 10.2174/0929867328666210629152929 -
Frontiers in Cellular and Infection... 2021Dengue fever (DF) is a mosquito-borne viral disease caused by the dengue virus (DENV), which is considered one of the most important arboviruses in the world. This study...
Dengue fever (DF) is a mosquito-borne viral disease caused by the dengue virus (DENV), which is considered one of the most important arboviruses in the world. This study aimed to determine the molecular, epidemiological, and phylogenetic characterization of 174 DENV-1 (132 indigenous cases and 42 imported cases) isolated from nine municipalities of Zhejiang province in 2019. The analyses of phylogenetics, haplotypes, and amino acid substitutions were conducted based on the full envelope (E) gene sequences. Sixty-four haplotypes were clustered into two main clades, with isolates from Wenzhou and Taizhou mainly clustered into clade I and Hangzhou and Ningbo cases clustered into clade II. Six sites of amino acid substitutions including A88T, F96L, M297V, T339S, I378L, and V436I were only observed in strains isolated from Ningbo and Hangzhou, while two sites of amino acid substitutions including V312L and V380I were observed in strains from Taizhou and Wenzhou. In our study, strains were in high homology with the strains from Southeast Asian countries, thus cases in Zhejiang were probably imported from Southeast Asian countries. The strains from different regions in Zhejiang were clustered in the same branch which may be caused by the continuous import of cases in the same country at different time periods. After the continuous outbreak in Zhejiang province, some sites of the dengue gene have mutated, and the effects need further study.
Topics: Animals; China; Dengue; Dengue Virus; Disease Outbreaks; Genotype; Phylogeny; Serogroup
PubMed: 34676175
DOI: 10.3389/fcimb.2021.673299 -
International Journal of Molecular... May 2023Dengue virus (DENV) is a single-stranded (+)-sense RNA virus that infects humans and mosquitoes, posing a significant health risk in tropical and subtropical regions....
Dengue virus (DENV) is a single-stranded (+)-sense RNA virus that infects humans and mosquitoes, posing a significant health risk in tropical and subtropical regions. Mature virions are composed of an icosahedral shell of envelope (E) and membrane (M) proteins circumscribing a lipid bilayer, which in turn contains a complex of the approximately 11 kb genomic RNA with capsid (C) proteins. Whereas the structure of the envelope is clearly defined, the structure of the packaged genome in complex with C proteins remains elusive. Here, we investigated the interactions of C proteins with viral RNA, in solution and inside mature virions, via footprinting and cross-linking experiments. We demonstrated that C protein interaction with DENV genomes saturates at an RNA:C protein ratio below 1:250. Moreover, we also showed that the length of the RNA genome interaction sites varies, in a multimodal distribution, consistent with the C protein binding to each RNA site mostly in singlets or pairs (and, in some instances, higher numbers). We showed that interaction sites are preferentially sites with low base pairing, as previously measured by 2'-acetylation analyzed by primer extension (SHAPE) reactivity indicating structuredness. We found a clear association pattern emerged: RNA-C protein binding sites are strongly associated with long-range RNA-RNA interaction sites, particularly inside virions. This, in turn, explains the need for C protein in viral genome packaging: the protein has a chief role in coordinating these key interactions, promoting proper packaging of viral RNA. Such sites are, thus, highly consequential for viral assembly, and, as such, may be targeted in future drug development strategies against these and related viruses.
Topics: Animals; Humans; Capsid Proteins; Dengue Virus; Genome, Viral; Capsid; RNA, Viral
PubMed: 37175867
DOI: 10.3390/ijms24098158 -
Pharmaceutical Patent Analyst Dec 2020Dengue, an illness caused by four serotypes of the dengue virus is most prevalent in Asia and Latin America. Its manifestation varies from asymptomatic cases to severe... (Review)
Review
Dengue, an illness caused by four serotypes of the dengue virus is most prevalent in Asia and Latin America. Its manifestation varies from asymptomatic cases to severe forms and even deaths and is a growing health concern. Despite attempts to curtail it, the infection continues to intensify in endemic areas and spread to new areas of the world. Development of a safe and effective vaccine and a potent antiviral drug is ongoing but so far there has been no breakthrough. Nonetheless, researchers are carrying out studies with newer vaccine candidates and antiviral moieties, and some of these hold promise for the future. The current article describes the recent patents targeted at dengue control.
Topics: Animals; Antiviral Agents; Dengue; Dengue Vaccines; Dengue Virus; Drug Development; Humans; Patents as Topic; Serogroup
PubMed: 33350353
DOI: 10.4155/ppa-2020-0012 -
EMBO Reports Nov 2022Frequent turnover of dengue virus (DENV) clades is one of the major forces driving DENV persistence and prevalence. In this study, we assess the fitness advantage of...
Frequent turnover of dengue virus (DENV) clades is one of the major forces driving DENV persistence and prevalence. In this study, we assess the fitness advantage of nine stable substitutions within the envelope (E) protein of DENV serotypes. Two tandem neighboring substitutions, threonine to lysine at the 226 (T226K) and glycine to glutamic acid at the 228 (G228E) residues in the DENV2 Asian I genotype, enhance virus infectivity in either mosquitoes or mammalian hosts, thereby promoting clades turnover and dengue epidemics. Mechanistic studies indicate that the substitution-mediated polarity changes in these two residues increase the binding affinity of E for host C-type lectins. Accordingly, we predict that a G228E substitution could potentially result in a forthcoming epidemic of the DENV2 Cosmopolitan genotype. Investigations into the substitutions associated with DENV fitness in hosts may offer mechanistic insights into dengue prevalence, thus providing a warning of potential epidemics in the future.
Topics: Animals; Dengue Virus; Dengue; Phylogeny; Serogroup; Genotype; Mutation; Mammals
PubMed: 36197120
DOI: 10.15252/embr.202255671 -
BMC Infectious Diseases Aug 2021Dengue fever is a mosquito born disease associated with self-limited to life threatening illness. First detected in Senegal in the nineteenth century, and despite its...
BACKGROUND
Dengue fever is a mosquito born disease associated with self-limited to life threatening illness. First detected in Senegal in the nineteenth century, and despite its growing incidence this last decade, significant knowledge gaps exist in our knowledge of genetic diversity of circulating strains. This study highlights the circulating serotypes and genotypes between January 2017 and December 2018 and their spatial and temporal distribution throughout all regions of Senegal.
METHODS
We used 56 dengue virus (DENV) strains for the analysis collected from 11 sampling areas: 39 from all regions of Senegal, and 17 isolates from Thiès, a particular area of the country. Two real time RT-qPCR systems were used to confirm dengue infection and corresponding serotypes. For molecular characterization, CprM gene was sequenced and submitted to phylogenetic analysis for serotypes and genotypes assignment.
RESULTS
Three dengue virus serotypes (DENV-1-3) were detected by all used methods. DENV-3 was detected in 50% (28/56) of the isolates, followed by DENV-1 and DENV-2, each representing 25% (14/56) of the isolates. DENV-3 belongs to genotype III, DENV-1 to genotype V and DENV-2 to Cosmopolitan genotype. Serotype 3 was detected in 7 sampling locations and a co-circulation of different serotypes was observed in Thiès, Fatick and Richard-toll.
CONCLUSIONS
These results emphasize the need of continuous DENV surveillance in Senegal to detect DENV cases, to define circulating serotypes/genotypes and to prevent the spread and the occurrence of severe cases.
Topics: Dengue; Dengue Virus; Humans; Phylogeny; Public Health Surveillance; Senegal; Serogroup; Spatial Analysis
PubMed: 34429064
DOI: 10.1186/s12879-021-06580-z -
Archives of Virology Apr 2021Dengue virus (DV) is a mosquito-borne virus that is endemic to many tropical and subtropical areas. Recently, the annual incidence of DV infection has increased...
Dengue virus (DV) is a mosquito-borne virus that is endemic to many tropical and subtropical areas. Recently, the annual incidence of DV infection has increased worldwide, including in Korea, due to global warming and increased global travel. We therefore sought to characterize the molecular and evolutionary features of DV-1 and DV-4 isolated from Korean overseas travelers. We used phylogenetic analysis based on the full coding region to classify isolates of DV-1 in Korea into genotype I (43251, KP406802), genotype IV (KP406803), and genotype V (KP406801). In addition, we found that strains of DV-4 belonged to genotype I (KP406806) and genotype II (43257). Evidence of positive selection in DV-1 strains was identified in the C, prM, NS2A, and NS5 proteins, whereas DV-4 showed positive selection only in the non-structural proteins NS2A, NS3, and NS5. The substitution rates per site per year were 5.58 × 10 and 6.72 × 10 for DV-1 and DV-4, respectively, and the time of the most recent common ancestor was determined using the Bayesian skyline coalescent method. In this study, the molecular, phylogenetic, and evolutionary characteristics of Korean DV-1 and DV-4 isolates were evaluated for the first time.
Topics: Amino Acid Sequence; Amino Acid Substitution; Base Sequence; Dengue; Dengue Virus; Evolution, Molecular; Genotype; Humans; Phylogeny; RNA, Viral; Republic of Korea; Selection, Genetic; Serogroup; Travel; Viral Proteins
PubMed: 33575893
DOI: 10.1007/s00705-021-04973-8