Search Results (1,022)

Aims: The screening and diagnosis of dengue virus infection play a crucial role in controlling the epidemic of dengue fever, highlighting the urgent need for a highly sensitive, simple, and rapid laboratory testing method. This study aims to assess the clinical performance of MAGLUMI Denv NS1 in detecting dengue virus NS1 antigen. Methods: A retrospective study was conducted to assess the sensitivity and specificity of MAGLUMI Denv NS1 using residual samples. Dengue-confirmed and excluded samples, validated by qPCR, were subjected to testing with MAGLUMI Denv NS1 in accordance with the manufacturer’s instructions. The linear range, endogenous interference, and cross-reactivity of MAGLUMI Denv NS1 were verified, and a consistency analysis with commercial comparator products was carried out. Results: The diagnostic specificity of MAGLUMI Denv NS1 is 98.41% (62/63), and the sensitivity is 98.32% (117/119). It effectively detects various serotypes of dengue virus, with no observed endogenous interference or cross-reactivity. Additionally, the consistency of NS1, IgM, and IgG tests on the MAGLUMI platform compared to commercial comparator reagents reaches 85.71%, 99.25%, and 98.97%, respectively. Conclusions: The MAGLUMI Denv NS1 represents a highly sensitive laboratory testing method capable of enhancing the diagnostic accuracy and efficiency of dengue virus infection detection. Full article

Flaviviruses are a diverse group of viruses primarily transmitted through hematophagous insects like mosquitoes and ticks. Significant expansion in the geographic range, prevalence, and vectors of flavivirus over the last 50 years has led to a dramatic increase in infections that can manifest as hemorrhagic fever or encephalitis, leading to prolonged morbidity and mortality. Millions of infections every year pose a serious threat to worldwide public health, encouraging scientists to develop a better understanding of the pathophysiology and immune evasion mechanisms of these viruses for vaccine development and antiviral therapy. Extensive research has been conducted in developing effective antivirals for flavivirus. Various approaches have been extensively utilized in clinical trials for antiviral development, targeting virus entry, replication, polyprotein synthesis and processing, and egress pathways exploiting virus as well as host proteins. However, to date, no licensed antiviral drug exists to treat the diseases caused by these viruses. Understanding the mechanisms of host–pathogen interaction, host immunity, viral immune evasion, and disease pathogenesis is highly warranted to foster the development of antivirals. This review provides an extensively detailed summary of the most recent advances in the development of antiviral drugs to combat diseases. Full article

Current arbovirus surveillance strategies in Australia involve mosquito collection, species identification, and virus detection. These processes are labour-intensive, expensive, and time-consuming and can lead to delays in reporting. Mosquito excreta has been proposed as an alternative sample type to whole mosquito collection, with potential to streamline the virus surveillance pipeline. In this study, we investigated the feasibility of Aedes aegypti excreta as a sample type in the detection of Dengue virus serotype 2 (DENV2). DENV2 could be detected from as little as one DENV2-infected mosquito excreta spot, with virus levels in individual excreta spots varying within and between mosquitoes and depending highly on mosquito viral load. Detectability was improved by pooling up to 20 DENV2-infected mosquitoes and collecting excreta into liquid substrate, followed by virus concentration using magnetic nanoparticles. Virus concentration improves quantification accuracy in comparison to unconcentrated samples and increases the amount of material available for detection, expanding detection capabilities to techniques with higher limits of detection. Mosquito excreta as a sample type, coupled with magnetic virus concentration, expands the current detection toolbox for DENV2 and has the potential to improve arbovirus surveillance strategies in Australia. Full article

With the advent of a variety of vaccines against viral infections, there are multiple viruses that can be prevented via vaccination. However, breakthrough infections or uncovered strains can still cause vaccine-preventable viral infections (VPVIs). Therefore, timely diagnosis, treatment, and surveillance of these viruses is critical to patient care and public health. Point-of-care (POC) viral diagnostics tools have brought significant improvements in the detection and management of VPVIs. These cutting-edge technologies enable prompt and accurate results, enhancing patient care by facilitating timely treatment decisions. This review delves into the advancements in POC testing, including antigen/antibody detection and molecular assays, while focusing on their impact on the diagnosis, treatment, and surveillance of VPVIs such as mpox, viral hepatitis, influenza, flaviviruses (dengue, Zika, and yellow fever virus), and COVID-19. The role of POC tests in monitoring viral infection is crucial for tracking disease progression and managing outbreaks. Furthermore, the application of POC diagnostics has shown to be vital for public health strategies. In this review, we also highlight emerging POC technologies such as CRISPR-based diagnostics and smartphone-integrated POC devices, which have proven particularly beneficial in resource-limited settings. We underscore the importance of continued research to optimize these diagnostic tools for wider global use for mpox, viral hepatitis, influenza, dengue, and COVID-19, while also addressing current challenges related to their sensitivity, specificity, availability, efficiency, and more. Full article

Every year, dengue virus affects hundreds of millions of individuals worldwide. To date, there is no specific medication to treat dengue virus infections. Nucleobases, the base of a nucleoside without ribose, are understudied as potential treatments for viral infections. Antiviral nucleobases are converted in infected cells to their corresponding nucleoside triphosphate active form. Importantly, the conversion of nucleobases to their active nucleotide form and their antiviral effect can be enhanced when combined with de novo nucleotide biosynthesis inhibitors. In this work, we evaluated seven purine and pyrimidine nucleobases alone or combined with six purine or pyrimidine de novo nucleotide biosynthesis inhibitors, including novel prodrugs. Our study revealed that while a strong potentiation of purine nucleobases by purine de novo nucleotide biosynthesis inhibitors was observed, the pyrimidine nucleobases were not potentiated by pyrimidine de novo nucleotide biosynthesis inhibitors, possibly highlighting a significant difference between the modulation of purine versus pyrimidine de novo pathways and their impact on nucleobase potentiation. Most significant antiviral effects and potentiation were observed for Favipiravir, T-1105, and ribavirin nucleobases combined with purine nucleotide de novo synthesis inhibitors. These results are significant because drug combinations may solve the limited efficacy observed for some antiviral nucleobase drugs such as Favipiravir. Full article

The dengue virus (DENV) is primarily transmitted by Aedes aegypti. Investigating genes associated with mosquito susceptibility to DENV2 offers a theoretical foundation for targeted interventions to regulate or block viral replication and transmission within mosquitoes. Based on the transcriptomic analyses of the midgut and salivary glands from Aedes aegypti infected with DENV2, alongside analyses of Aag2 cell infections, 24 genes potentially related to the regulation of Aedes aegypti infection with DENV2 were selected. By establishing transient transfection and overexpression models of Aedes aegypti Aag2 cells, and mosquito target gene interference models, the difference in viral load before and after treatment was compared, and the effects of DEGs on viral replication were evaluated. After overexpressing 24 DEGs in Aag2 cells, 19 DEGs showed a significant difference in DENV2 RNA copies in the cell supernatant (p < 0.05). In adult mosquitoes, knocking down defensin-A, defensin-A-like, and SMCT1 respectively reduced the DENV2 RNA copies, while knocking down UGT2B1 and ND4 respectively increased the DENV2 RNA copies. In this study, to assess the role of genes related to DENV2 replication, and transient transfection and overexpression models in Aag2 cells and mosquito gene knockdown models were established, and five genes, defensin-A, defensin-A-like, SMCT1, UGT2B1, and ND4, were found to have an impact on the replication of DENV2, providing a reference basis for studying the complex mechanism of mosquito–virus interactions. Full article

Dengue fever, caused by the dengue virus (DENV), poses a significant global health challenge, particularly in tropical and subtropical regions. Recent increases in indigenous DENV cases in Europe are concerning, reflecting rising incidence linked to climate change and the spread of Aedes albopictus mosquitoes. These vectors thrive under environmental conditions like temperature and humidity, which are increasingly influenced by climate change. Additionally, global travel accelerates the cross-border spread of mosquito-borne diseases. DENV manifests clinically in a spectrum from asymptomatic cases to severe conditions like dengue hemorrhagic fever and dengue shock syndrome, influenced by viral serotype and host factors. In 2024, Brazil experienced a fourfold increase in dengue cases compared to 2023, accompanied by higher mortality. Conventional control measures, such as vector control, community engagement, and vaccination, proved insufficient as climate change exacerbated mosquito proliferation, challenging containment efforts. In this regard, our review analyzes prevention measures and therapeutic protocols during the outbreak while addressing DENV transmission dynamics, clinical presentations, and epidemiological shifts. It also evaluates diagnostic strategies combining clinical assessment with serological and molecular testing, providing information to improve diagnostic and preventive measures. The global expansion of dengue-endemic regions, including outbreaks in Europe, highlights the urgent need for enhanced surveillance, proactive interventions, and international collaboration to mitigate the growing threat of Dengue and other arboviruses like West Nile, Zika, Chikungunya, Oropouche, and Yellow Fever viruses. Full article

Dengue, West Nile, Zika, Yellow fever, and Japanese encephalitis viruses persist as significant global health threats. The development of new therapeutic strategies based on inhibiting essential viral enzymes or viral–host protein interactions is problematic due to the fast mutation rate and rapid emergence of drug resistance. This study focuses on the NS2B-NS3 protease as a promising target for antiviral drug development. Promising allosteric binding sites were identified in two conformationally distinct inactive states and characterized for five flaviviruses and four Dengue virus subtypes. Their shapes, druggability, inter-viral similarity, sequence variation, and susceptibility to drug-resistant mutations have been studied. Two identified allosteric inactive state pockets appear to be feasible alternatives to a larger closed pocket near the active site, and they can be targeted with specific drug-like small-molecule inhibitors. Virus-specific sequence and structure implications and the feasibility of multi-viral inhibitors are discussed. Full article

Flaviviruses are arthropod-borne viruses primarily transmitted through the mosquito Aedes aegypti or Culex genus of mosquitos. These viruses are predominantly found in tropical and subtropical regions of the world with their geographical spread predicted to increase as global temperatures continue to rise. These viruses cause a variety of diseases in humans with the most prevalent being caused by dengue, resulting in hemorrhagic fever and associated sequala. Current approaches for therapeutic control of flavivirus infections are limited, and despite recent advances, there are no approved drugs. Vaccines, available for a few circulating flaviviruses, still have limited potential for controlling contemporary and future outbreaks. Mouse models provide us with a valuable tool to test the effectiveness of drugs and vaccines, yet for many flaviviruses, well-established mouse models are lacking. In this review, we highlight the current state of flavivirus vaccines and therapeutics, as well as our current understanding of mouse models for various flaviviruses. Full article

The dengue virus (DENV) is a mosquito-borne flavivirus endemic to many tropical and subtropical regions. Over the past few decades, the global incidence of dengue has risen dramatically, with the virus now present in over 100 countries, putting nearly half of the world’s population at risk. This increase is attributed to several factors, including urbanization, climate change, and global travel, which facilitate the spread of both the virus and its mosquito vectors. While dengue is primarily associated with tropical regions, outbreaks in temperate areas are becoming increasingly common due to the spread of Aedes albopictus, a competent vector for DENV that can adapt to cooler climates. This study investigates the molecular dynamics and geographic evolution of DENV type 1 (DENV-1) strains isolated from 13 patients during an autochthonous outbreak in Lombardy, Northern Italy, between August and September 2023. Additionally, Aedes albopictus mosquitoes were collected from a neighboring area to assess their potential role in the outbreak. A metagenomic approach was used to recover DENV-1 consensus sequences from clinical samples. Genotype classification and phylogenetic analyses were performed using Bayesian methods and a comprehensive dataset of DENV-1 sequences from other countries. The Italian autochthonous strains clustered with South American strains collected between 2020 and 2023, specifically those belonging to genotype V, subtype D. Bayesian analysis estimated a mean evolutionary substitution rate of 8.234 × 10⁻⁴ substitutions per site per year (95% HPD interval: 7.1448 × 10⁻⁴–9.3343 × 10⁻⁴), with the time to the most recent common ancestor (tMRCA) dating back to 1972 (95% HPD interval: 1968–1976). These findings suggest the likely introduction of the virus into the region from endemic areas in South America, followed by local transmission. This study offers valuable insights into the dynamics of the DENV-1 outbreak in Lombardy, underscoring the importance of genomic surveillance in monitoring viral spread and evolution. The findings emphasize the critical need for enhanced molecular and entomological surveillance to detect and respond to emerging autochthonous DENV cases in temperate regions where competent vectors, such as Aedes albopictus, are present. Public health strategies should prioritize integrated vector management, real-time genomic monitoring, and awareness campaigns to mitigate the risk of future outbreaks. These measures are essential to address the growing threat posed by the geographic expansion of the dengue virus. Full article

Viruses transmitted by arthropods (arboviruses) pose a global public health threat. Sporadic cases or outbreaks caused by West Nile virus, Crimean–Congo haemorrhagic fever virus, tick-borne encephalitis virus, and phleboviruses are often reported in Europe. Recently, they expanded their distribution in geographic areas where they had never been observed before, while tropical viruses, like Dengue, Chikungunya, and Zika, started to cause autochthonous cases and outbreaks following the return of viraemic travellers from endemic countries. The primary or secondary vectors of these viruses are established in Europe, and the incidence of arboviral diseases is expected to increase due to several anthropogenic and/or environmental factors (mainly climate change, which affects the survival and amplification of the arthropod vectors). This is an update on the emerging arboviruses in Europe, associated challenges, and future perspectives. Full article

This study investigated a library of known and novel glycyrrhizic acid (GL) conjugates with amino acids and dipeptide esters, as inhibitors of the DENV NS2B-NS3 protease. We utilized docking algorithms to evaluate the interactions of these GL derivatives with key residues (His51, Asp75, Ser135, and Gly153) within 10 Å of the DENV-2 NS2B-NS3 protease binding pocket (PDB ID: 2FOM). It was found that compounds 11 and 17 exhibited unique binding patterns, forming hydrogen bonds with Asp75, Tyr150, and Gly153. Based on the molecular docking data, conjugates 11 with L-glutamic acid dimethyl ester, 17 with β-alanine ethyl ester, and 19 with aminoethantic acid methyl ester were further demonstrated as potent inhibitors of DENV-2 NS3 protease, with IC50 values below 1 μM, using NS3-mediated cleavage assay. Compound 11 was the most potent, with EC50 values of 0.034 μM for infectivity, 0.042 μM for virus yield, and a selective index over 2000, aligning with its strong NS3 protease inhibition. Compound 17 exhibited better NS3 protease inhibition than compound 19 but showed weaker effects on infectivity and virus yield. While all compounds strongly inhibited viral infectivity post-entry, compound 19 also blocked viral entry. This study provided valuable insights into the interactions between active GL derivatives and DENV-2 NS2B-NS3 protease, offering a comprehensive framework for identifying lead compounds for further drug optimization and design as NS2B-NS3 protease inhibitors against DENV. Full article

Antibody-dependent enhancement (ADE) is a phenomenon in which antibodies enhance subsequent viral infections rather than preventing them. Sub-optimal levels of neutralizing antibodies in individuals infected with dengue virus are known to be associated with severe disease upon reinfection with a different dengue virus serotype. For Severe Acute Respiratory Syndrome Coronavirus type-2 infection, three types of ADE have been proposed: (1) Fc receptor-dependent ADE of infection in cells expressing Fc receptors, such as macrophages by anti-spike antibodies, (2) Fc receptor-independent ADE of infection in epithelial cells by anti-spike antibodies, and (3) Fc receptor-dependent ADE of cytokine production in cells expressing Fc receptors, such as macrophages by anti-nucleocapsid antibodies. This review focuses on the Fc receptor-dependent ADE of cytokine production induced by anti-nucleocapsid antibodies, examining its potential role in severe COVID-19 during reinfection and its contribution to the post-acute sequelae of COVID-19, i.e., prolonged symptoms lasting at least three months after the acute phase of the disease. We also discuss the protective effects of recently identified anti-spike antibodies that neutralize Omicron variants. Full article

In 2023, one case of coinfection with type I and type II dengue virus of imported origin was first reported in Jiaxing city. Therefore, we analysed the results of the molecular tracing analysis of this case. We collected serum samples for whole-genome amplification and sequencing and further analysed the whole-genome sequence for homology analysis, evolutionary tree analysis, and protein amino acid mutation site analysis. The results revealed that the JX202301 DENV-1 sequence had the highest homology with the epidemic strains in Guangdong (PP563909, PP563875, PP563840, and PP563879) in 2023, with nucleotide homology ranging from 99.5 to 99.8% and amino acid homology of 100%. The JX202301 DENV-2 sequence had the highest homology with the epidemic strains of 2019 Thailand (MZ636805, MZ636802, MZ636803, MW512454, and MW512419), with nucleotide homology ranging from 98.4 to 99.2% and amino acid homology of 99.7%. By analysing the amino acid mutation sites, we found that, compared with the corresponding reference strains and the epidemic strains in the same branch, there were 52 amino acid difference sites in the viral coding region of the DENV-1 sequence and 51 amino acid difference sites in the viral coding region of the DENV-2 sequence, which were mainly concentrated in the NS1 and NS5 region of the nonstructural proteins. In this study, we described for the first time the genome-wide sequence, genetic variation, and phylogenetic analysis of imported DENV-1 and DENV-2 mixed cases in Jiaxing city. These results provide a scientific basis for dengue fever outbreak surveillance, viral evolution studies, and prevention and control strategy development in Jiaxing city. Full article

The SARS-CoV-2 pandemic has significantly impacted global health and has led the population and the scientific community to live in fear of a future pandemic. Based on viral infectious diseases, innate immunity cells such as mast cells and basophils play a fundamental role in the pathogenesis of viral diseases. Understanding these mechanisms could be essential to better study practical therapeutic approaches not only to COVID-19 but also to other viral infections widely spread worldwide, such as influenza A, HIV, and dengue. In this literature review, we want to study these concepts. Mast cells and basophils intervene as a bridge between innate and acquired immunity and seem to have a role in the damage mechanisms during infection and in the stimulation of humoral and cellular immunity. In some cases, these cells can act as reservoirs and favor the replication and spread of the virus in the body. Understanding these mechanisms can be useful not only in therapeutic but also in diagnostic and prognostic perspectives. The prospects of applying artificial intelligence and machine learning algorithms for the creation of very accurate diagnostic/prognostic tools are interesting. Full article