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Precision repurposing of clinically characterized molecules targeting dengue virus RNA-dependent RNA polymerase: an in silico identification and in vitro validation.

The dengue virus has developed an effective replication mechanism that enables rapid viral replication in human hosts. The use of a molecular bottleneck offers an ideal approach for antiviral intervention, especially when no clinically authorized antivirals are available against dengue. The replication process is challenging due to functional redundancy. One of the core antiviral targets is the viral RNA-dependent RNA polymerase (RdRp), a conserved and essential component of the DENV replication machinery with no mammalian homolog, which represents a promising target for antiviral intervention…

Repurposing of FDA-approved drugs to identify potential ns2b/ns3 protease inhibitors against dengue virus: In silico and in vitro evaluation.

Dengue virus (DENV) poses a significant global health burden, affecting many countries and regions worldwide, with no specific antiviral therapy currently available. The NS2B/NS3 protease is a crucial enzyme in viral replication, making it a promising target for the development of antiviral drugs. Drug repurposing offers a rapid and cost-efficient strategy by evaluating FDA-approved compounds for new antiviral indications. The present study aimed to identify potent inhibitors of DENV-2 NS2B/NS3 protease with an integrated in silico and in vitro analysis. Molecular docking was used to screen a …

Dengue viruses serotypes 2 and 4 exhibit distinct infection kinetics and modulation of anti-viral immune responses in human tonsil histocultures.

Dengue virus (DENV) is the most prevalent mosquito-borne viral disease with over ten million cases worldwide. There are four antigenically distinct, co-circulating DENV serotypes (DENV 1-4) capable of infecting humans. Given the lack of immunocompetent animal models and the limitations of known cell culture models, more physiologically relevant experimental models are needed to recapitulate DENV infection and host immune responses. Building on previous observations that DENV-2 and DENV-4 serotypes elicit distinct innate immune responses in monocyte-derived dendritic cells (moDC) in vitro, we u…

Cutaneous Manifestations of Emerging Arbovirus Infections Including West Nile, Dengue, Zika, Chikungunya, Usutu, and Toscana Viruses: A Clinical Overview for Dermatologists.

Arboviral infections, notably those caused by West Nile virus (WNV), Dengue virus (DENV), Zika virus (ZIKV), and Chikungunya virus (CHIKV), represent a growing global health concern due to their expanding geographic distribution and evolving clinical spectrum. While systemic and neurologic complications are well recognized, cutaneous manifestations are frequently overlooked despite their diagnostic and prognostic value. These viruses, transmitted primarily by Aedes or Culex mosquitoes, share overlapping symptoms such as fever, headache, arthralgia, myalgia, and malaise but can often be disting…

Arbovirus Outbreak Reveals Co-Infection of Dengue and Chikungunya Viruses at Zona da Mata Region in Minas Gerais, Brazil, During 2024.

OBJECTIVES: To characterise the recent circulation of dengue and chikungunya viruses in the Zona da Mata region of Minas Gerais, Brazil, during the major arbovirus epidemic of 2024, using publicly available RT-qPCR test results. METHODS: We analysed data from DATASUS obtained by RT-qPCR tests for dengue, Zika and chikungunya viruses reported between January and September 2024 across 41 municipalities. Demographic and epidemiological patterns were assessed, including virus-specific incidence, re-infection, sequential infection and co-infection events, and associations with testing effort. RES…

Молекулярные данные о совместном циркуляции различных серотипов вируса денге, связанных с одновременной инфекцией малярии среди фебрильных детей в Либревиле, Габон.

ЦЕЛЬ: Острые фебриальные заболевания часто объясняются малярией в эндемических странах, несмотря на циркуляцию арбовирусов, у переносчиков которых одна и та же среда размножения. В ходе этого исследования была проведена оценка молекулярной распространенности сопутствующих инфекций арбовира и арбовира-малярии, а также связанных с этим эпидемиологических и гематологических характеристик среди фебрильных детей в Либревиле, Габон. МЕТОДЫ: В период с сентября по октябрь 2022 года были ретроспективно проанализированы образцы плазмы у 151 ребенка-фебрила, посещавшего район наблюдения за малярией. Про

Совпадение в аннотации оригинала
OBJECTIVE: Acute febrile illnesses are frequently attributed to malaria in endemic countries, despite the circulation of arboviruses whose v … sible DENV-4. No CHIKV or ZIKV infections were detected. Malaria prevalence was 56.9%, and 9.3% had dengue-malaria co-infection. Dengue predominated in children <5 years, whereas those aged 5-10 years had higher odds of malaria (OR: 2.61 IC95%: [1.07-7.02]; p=0.03) and co-infection (OR:16.28 IC95% [1.85-79.40]; p=0.002). DENV infections occurred mainly i …

Integrated validation of internally controlled one-step multiplex real-time RT-PCR for dengue virus serotyping and monoplex assay for quantification.

Dengue is a major global health challenge, yet no commercially validated molecular kits currently provide both serotyping and viral load quantification in a single integrated format. To address this gap, we developed and internally validated a one-step multiplex real-time RT-PCR assay that simultaneously detects all four dengue virus (DENV) serotypes in a single reaction (5-PLEX), together with a complementary monoplex system for quantitative viral load measurement. The 5-PLEX assay demonstrated high specificity and reliable serotyping performance during acute and early critical phases of deng…

Interactions between mosquito genetic background and Wolbachia strain affect dengue virus blocking and fitness in South American populations of Aedes aegypti.

The mosquito Aedes aegypti is the primary vector of dengue virus, and the release of mosquitoes infected with the bacterium Wolbachia is an increasingly used strategy to reduce dengue transmission. This approach relies on Wolbachia's ability to suppress virus replication within the mosquito, but the effectiveness of virus suppression and the associated fitness costs may depend on interactions among mosquito genetic background, Wolbachia strain, and dengue virus type. Here, we examined these interactions using mosquito populations from Brazil, Paraguay, and Peru infected with two Wolbachia stra…

Point-of-care dengue detection in Indonesia: Locally assembled NS1 and IgM combination rapid diagnostic tests (RDTs) as a promising approach.

Dengue infection remains a major public health concern in Indonesia. Rapid and valid dengue virus (DENV) diagnosis is critical to prompt care and intervention. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), as the gold standard, is challenging to implement in fast-paced settings with limited resources. Therefore, rapid diagnostic tests (RDTs) offer a practical and simpler alternative with differing accuracy. This study aims to compare RDTs' performance with RT-qPCR using specimens of dengue-suspected patients from two hospitals in North Jakarta. A total of 111 archived…

Epitope dynamics and antigenic shifts in dengue virus serotype 2 cosmopolitan genotype with structural changes in Bangladesh from 2017 to 2023.

Dengue Virus Serotype 2 (DENV-2) is increasingly impacting public health, especially in South and Southeast Asia. Bangladesh faced its most severe dengue outbreak in 2023, reporting 318,623 cases and over 1,700 deaths, with the DENV-2 Cosmopolitan genotype responsible for 70.2% of cases. To better understand this event, we utilized in silico methods to explore mutational trends and epitope dynamics in global and Bangladeshi sequences from 2017 to 2023. The study aimed to provide insights into viral evolution and hypothesize how specific mutations might theoretically affect immune recognition. …

Warfarin-induced skin necrosis concurrent with dengue fever: a case report highlighting diagnostic and management challenges in a conflict-affected region.

Warfarin-induced skin necrosis (WSN) is a rare but serious complication of anticoagulation therapy. This case report describes a 34-year-old male with mechanical heart valves on long-term warfarin therapy who developed WSN after self-medicating with a doubled warfarin dose following a two-week interruption due to limited healthcare access in a conflict-affected region. Concurrently, he was diagnosed with dengue fever, further complicating anticoagulation management due to thrombocytopenia. Prompt discontinuation of warfarin, intravenous vitamin K administration, and delayed initiation of enoxa…

Computational Cross-Aggregation Study of Dengue Virus NS1, Capsid Anchor and 2k Peptides With Human Amylin, Aβ42 and α-Synuclein Peptides.

Dengue virus, an arbovirus, is the causal factor of thousands of deaths around the globe, although the long-term consequences of the same have not been elucidated in great detail. The virus encodes for a polyprotein, which is later cleaved to form multiple proteins, of which NS1 protein oligomerization domain, 2k, and capsid anchor are three aggregation-prone peptides, as have been previously seen. A relatively under-studied angle of these peptides is the role of these peptides in cross-aggregation with certain human aggregation-prone proteins. Here, we have tried to shed light on this cross-a…

Epidemiological Trends and Public Health Implications of Dengue Fever in Zhejiang Province, China: A Decadal Analysis from National to Cangnan Perspectives.

OBJECTIVE: To analyze dengue fever outbreaks in China, Zhejiang Province, and a local region to provide a scientific basis for early warning surveillance and the prevention and control of dengue epidemics. METHODS: This retrospective study examines dengue fever data from China and Zhejiang Province over the past decade, including incidence, mortality, seasonal distribution, age characteristics, and regional distribution. Local data from the past decade were also analyzed. RESULTS: Over the last ten years, the average annual incidence rate of dengue fever in China has been 0.7764 per 100,000 …

Temporal associations between microclimate, adult Aedes mosquito indices, and dengue cases at the residence level in Malaysia: Implications for targeted interventions.

INTRODUCTION: Dengue continues to be a major public health concern in Malaysia, as evidenced by the significant surge in cumulative dengue case numbers and deaths in 2023 compared to the previous year. While previous studies have explored the interplay of abiotic and biotic factors of mosquito density and dengue cases on a local scale in Malaysia, there is a notable gap in the research focusing on adult Aedes mosquito populations. AIMS: This study aims to contribute to the existing knowledge by investigating the association and time lags (TLs) between daily microclimate (DM), mosquito indices…

Genetic structure and knockdown resistance (kdr) mutations in Aedes albopictus (Skuse) (Diptera: Culicidae): Implications for dengue fever transmission in southeastern China.

Dengue fever, transmitted by Aedes albopictus in China, is a major public health issue. The emergence of kdr gene mutations in Ae. albopictus has reduced the efficacy of insecticide-based control. We investigated the genetic structure of eight Ae. albopictus populations from China's southeastern coastal region, analyzing genetic diversity, population structure, and the prevalence of kdr mutations in relation to dengue fever incidence. Allelic diversity was moderate, with the number of alleles ranging from 2 to 6 and effective number of alleles from 1.52 to 5.00. Genetic clustering revealed fou…

Efficacy of essential oil from Maranta arundinacea L. against immature stages of dengue, filariasis, and malaria vectors and four mosquito predators.

Mosquitoes are significant vectors of infectious diseases, causing thousands of fatalities worldwide each year. This present study was to check the toxicity of essential oil (EO) from Maranta arundinacea L. against three mosquito species: Anopheles stephensi, Culex quinquefasciatus and Aedes aegypti. The immature stages were exposed to five different concentrations such as 3.125, 6.25, 12.5, 25 and 50 ppm; these were used to check the insecticidal activity according to WHO standard protocol with slight modification. The EO presented 100 % ovicidal toxicity against the eggs of treated three mos

Assessing Aedes mosquito larval indicators, dengue virus infection rates, and risk factors in Khyber Pakhtunkhwa: Insights for improved vector control strategies.

BACKGROUND: Effective dengue management hinges on targeting key vector breeding sites and understanding transmission risks. Despite recurring outbreaks in Pakistan's Khyber Pakhtunkhwa (KP) Province since 2013, comprehensive entomological and virological data remain scarce. This study identified key larval-based indicators (habitats, Stegomyia indices), mosquito species composition, and dengue virus (DENV) infection rates in Aedes mosquitoes, evaluating their contributions to outbreak risk. METHODOLOGY/PRINCIPAL FINDINGS: From July to December 2021, a cross-sectional larval survey of Aedes ae…

Conspiracy Beliefs, Secondary Risk Perceptions, and Conditional Acceptance of Dengue Vaccine: A Multigroup Comparison Based on Prior COVID-19 Vaccination Experiences.

This study investigates the pathways linking general vaccine conspiracy beliefs to the conditional acceptance of the dengue vaccine, with a particular focus on the mediating role of secondary risk perceptions and the spillover effects of prior COVID-19 vaccination experiences. Based on an online survey of 1,001 Singaporeans and permanent residents, we found that stronger vaccine conspiracy beliefs were associated with heightened perceptions of secondary risk severity and susceptibility related to dengue vaccination, which, in turn, were linked to less favorable attitudes toward the dengue vacc…

Immunogenicity and safety of the live-attenuated tetravalent dengue vaccine (TAK-003) co-administered with recombinant 9-valent human papillomavirus vaccine.

BACKGROUND: The tetravalent dengue vaccine TAK-003 and the 9-valent human papillomavirus (9vHPV) vaccine regimens are potentially compatible, with overlapping target age groups, facilitating inclusion of TAK-003 into established immunization programs. METHODS: This phase 3, open-label, randomized, multicenter trial was conducted in Thailand to investigate the immunogenicity and safety of co-administration of TAK-003 with 9vHPV in healthy participants aged ≥9 to <15 years. Participants were randomized 1:1 to either Group 1 (9vHPV + TAK-003 Month [M]0, TAK-003 M3, 9vHPV M6) or Group 2 (9vHPV M0…