Search Results (2,408)

Background/Objectives: The coronavirus disease 2019 (COVID-19) pandemic profoundly disrupted global respiratory virus circulation, with sharp declines during 2020–2021, followed by a resurgence after the relaxation of public health measures. In South America, post-pandemic respiratory virus dynamics remain insufficiently characterized, particularly in ecologically diverse regions. Arequipa, a high-altitude city in southern Peru, has unique environmental conditions, including marked seasonal temperature variability, that may influence viral transmission. Methods: We performed a cross-sectional analysis of 21,784 nasopharyngeal swabs collected from symptomatic patients at four major hospitals between June 2021 and September 2023. All samples were tested for SARS-CoV-2 by RT-qPCR. Because routine screening for other respiratory viruses was implemented only in SARS-CoV-2-negative cases during the study period, a subset of SARS-CoV-2-negative samples was subsequently analyzed for influenza A virus (IAV), influenza B virus (IBV), and respiratory syncytial virus (RSV) using VIASURE assays. Viral circulation patterns were evaluated by year, month, and epidemiological week. Meteorological data were obtained from the SENAMHI–La Pampilla station. Logistic regression models were used to assess epidemiological and climatic predictors of viral detection. Results: SARS-CoV-2 positivity declined from 20.0% in 2021 to 8.8% in 2023. Conversely, detection of other respiratory viruses among SARS-CoV-2-negative samples increased from 0.8% in 2021 to 29.0% in 2023 (p < 0.01). Temporal increases in detection were observed during 2022–2023, particularly for IAV and RSV. In exploratory analyses, calendar year and relative humidity were associated with IAV and RSV detection, while age and temperature variables were associated with IBV. Conclusions: Climatic and demographic variables were associated with changes in viral detection for IAV, IBV, and RSV during the post-pandemic transition period in Arequipa. These findings describe patterns of viral detection within SARS-CoV-2-negative symptomatic patients and should be interpreted as surveillance-based observations rather than population-level estimates. Strengthened integrated epidemiological and genomic surveillance will be essential for vaccine planning and outbreak preparedness in the post-pandemic era. Full article

This review critically examines the inhibition of viral entry as an emerging disease-modifying strategy in chronic hepatitis B (HBV) and delta (HDV) virus infection, with particular emphasis on bulevirtide, the first-in-class of the sodium taurocholate cotransporting polypeptide entry inhibitor. This paper summarizes the analysis of 7 clinical trials that either underpinned the registration of bulevirtide or are important European real-life trials. We synthesize virological, pathophysiological and clinical evidence, highlighting the impact of this novel bulevirtide-based therapy on virological control, liver inflammation, fibrosis dynamics and long-term prognosis, as well as the limitations of this therapy. The observation of these trials is a greater than 2 log decrease from baseline in hepatitis D virus ribonucleic acid (HDV RNA) in 54–92% of patients and normalization of alanine transaminase (ALT) in 48.8–74% of patients after 23–144 weeks of treatment, and a significant decrease in liver fibrosis, as quantified by Fibroscan, at 12 months of treatment. The conclusion of the study is that this therapy represents an important leap in the etiological approach to chronic HDV infection and in improving the prognosis of these patients, but future clinical studies are needed to define the criteria for discontinuation of therapy, the long-term impact, as well as studies targeting new therapies that can intervene in other stages of the HDV and HBV life cycle not only to achieve HDV RNA negativity but also HBsAg clearance. Full article

SARS-CoV-2 infection has emerged worldwide. To reduce the number of cases and limit the transmission of the virus, health and local authorities have implemented several strategies. Mass screening is a key strategy for mitigating the damage caused by this pandemic. This strategy is based on the use of qRT-PCR and pooling to diagnose SARS-CoV-2 infection. The present work explores the performance and limitations of this strategy for the molecular diagnosis of SARS-CoV-2 infection. Three important technical aspects were retained: the comparison of two commercial extraction kits (BIGFISH and BIOER), the simulation of a non-compliant nasopharyngeal swab, and the evaluation of the pooling strategy. A total of 97 SARS-CoV-2-positive nasopharyngeal samples were used. The comparison of the two extraction kits was based on threshold cycles (Ct) values. The results showed a significant difference (IC = 95%) in the Ct of the nucleocapsid gene (N; p = 0.0000384) and RNA-dependent RNA polymerase (RdRp; p = 0.0254). However, no significant difference was observed between the Internal Control gene (IC; p = 0.0723) and Envelope gene (E; p = 0.150). The Ct values resulting from the BIGFISH extraction kit were generally lower than those obtained from BIOER. In terms of sensitivity, the RT-qPCR technique allows for the detection of viral RNA up to 10⁻³ as a dilution factor. This study demonstrated that the pooling strategy is an effective diagnostic technique. Positive samples remained detectable even in pools of 1000 or even 10,000 samples. However, the size of the pool under diagnostic conditions should not exceed a limit that must be dynamically adapted to prevalence to ensure economic and analytical viability. Full article

Hepatitis E virus (HEV) is a zoonotic pathogen of global concern that circulates in both domestic and wild swine populations. Understanding its presence and dynamics in wildlife reservoirs is crucial for assessing spillover risks and designing One Health surveillance strategies. This study investigated the occurrence, genetic diversity, and evolutionary relationships of HEV in wild boars from mainland Portugal. A total of 120 animals from seven districts were tested, with HEV RNA detected in four cases (3.3%), all from the Évora district near the Spanish border. One positive sample was successfully sequenced, and phylogenetic analysis based on the complete genome classified it within the HEV-3m subtype, clustering with predominantly human-derived sequences from Spain and France, which highlights its zoonotic potential. A second phylogenetic analysis based on a partial genomic fragment, including sequences from domestic pigs in Portugal, revealed the co-circulation of subtypes 3e, 3f, and 3m without clear spatial or temporal patterns. Phylogeographic analysis suggested that the identified strain was most likely introduced from Spain, supporting the hypothesis of cross-border transmission through wild boar movement. No recombination events were detected in the sequence obtained in this study. These findings provide the first molecular evidence of HEV-3m circulation in wild boars in Portugal, offering valuable insight into the HEV strain circulation in European wildlife populations. The zoonotic potential of HEV and the likelihood of interspecies transmission highlight the need for coordinated cross-border surveillance and integrated One Health strategies. Full article

Accurate forecasting of respiratory virus-associated hospitalization rates per 100,000 population is essential for healthcare capacity planning, yet remains challenging during the COVID-19 era due to abrupt distribution shifts and symptom overlap among influenza-like illnesses caused by multiple pathogens. We propose a two-stage deep learning framework that disentangles stable pre-pandemic seasonal dynamics from COVID-19-induced excess hospitalizations. A lightweight GRU is first trained on pre-pandemic surveillance data to model baseline influenza/RSV-driven seasonality, after which an excess model learns from the residual series and integrates multiple online search trends (flu, COVID-19, and fever) using a standard multi-head self-attention mechanism. While we use COVID-19-era data as a case study, the proposed baseline–excess decomposition is not disease-specific and is intended to generalize to future large-scale respiratory outbreaks or pandemics that induce abrupt regime shifts. Experiments on U.S. weekly respiratory hospitalization rate data curated from CDC surveillance networks (AME) show that the proposed approach achieves strong accuracy on a chronological COVID-era split (2020–2025), reaching $R^2=0.907$ with MAPE = 19.22%. Beyond point forecasts, we further evaluate an expanding-window rolling-origin protocol and report calibrated prediction intervals via split conformal prediction, supporting deployment-oriented uncertainty quantification. By decoupling baseline and excess components and fusing behavioral trend signals in a disciplined manner, this framework improves predictive performance under regime shift while providing interpretable excess estimates for timely situational awareness and healthcare resource planning. Full article

Monkeypox (Mpox), caused by the monkeypox virus (MPXV), has re-emerged as a significant global public health concern, particularly following the 2022 outbreaks. Understanding its transmission dynamics is essential for designing effective control strategies. In this study, we develop and analyze a deterministic compartmental model that captures both human-to-human and rodent-to-human transmission pathways in order to better reflect the zoonotic nature of the disease. The model is investigated using qualitative and quantitative analytical techniques, including stability analysis, bifurcation theory, and sensitivity analysis. The basic reproduction number, $R_0$, is derived and used to determine threshold conditions for disease persistence or eradication. We show that the disease-free equilibrium is globally asymptotically stable when $R_0<1$, while an endemic equilibrium exists and is stable when $R_0>1$. Furthermore, the model exhibits backward bifurcation, indicating that reducing $R_0$ below unity may not be sufficient for disease elimination. Sensitivity analysis identifies key parameters driving transmission, particularly the rodent-to-human and human-to-human contact rates. Numerical simulations further demonstrate that reducing cross-species transmission and improving isolation of infected individuals significantly decrease disease burden. These findings highlight the complexity of Mpox transmission and emphasize that effective control requires not only lowering $R_0$, but also targeting critical transmission pathways. This study provides useful insights for public health planning by identifying priority intervention strategies such as minimizing rodent–human interactions and strengthening isolation measures. Full article

Respiratory syncytial virus (RSV) is a major pathogen responsible for severe lower respiratory tract infections in infants, the elderly, and immunocompromised individuals. Because the RSV F protein mediates viral entry and 15-lipoxygenase (15-LOX) amplifies virus-induced inflammatory responses, dual targeting of these proteins may provide both antiviral and anti-inflammatory benefits. In this study, we combined computational prediction with experimental validation to identify natural dual-target inhibitors from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP). A total of 13,131 natural compounds were screened by drug-likeness evaluation, molecular docking, ADME assessment, and molecular dynamics simulations, yielding 31 potential dual-target candidates with favorable drug-like properties. Among them, rhoeadine (MOL001473) maintained stable binding conformations with both targets throughout 100 ns simulations. In BEAS-2B cells, rhoeadine exhibited significant anti-RSV activity (EC50 = 1.82 µM), low cytotoxicity (IC50 = 34.50 µM), and a selectivity index (SI) of 18.97. Time-of-addition experiments suggested that rhoeadine primarily acts at the early stage of viral infection. Additionally, ELISA results indicated that rhoeadine significantly inhibited RSV-induced secretion of CCL5 and IL-6, highlighting its anti-inflammatory potential. In summary, this study identified rhoeadine as a promising natural compound with antiviral and anti-inflammatory activities against RSV. Computational analyses suggested its potential association with RSV F protein and 15-LOX, although direct target-level validation is still required. Full article

Chandipura virus (CHPV) is a neurotropic rhabdovirus associated with recurrent outbreaks of acute encephalitis in children and a high case fatality rate, particularly in India. Despite its public health relevance, the host molecular processes governing CHPV infection and disease progression remain poorly defined. To address this gap, we conducted a time-resolved transcriptomic analysis to characterize host responses to CHPV infection and to explore host-directed therapeutic opportunities. Human HEK293T cells were infected with CHPV, followed by RNA sequencing (RNA-seq) at 6, 12, 18, and 24 h post infection (hpi). Transcriptome profiling revealed a temporally ordered host response. At 6 hpi, CHPV infection was dominated by strong activation of innate immune and inflammatory pathways, including interferon-stimulated genes and cytokine signaling. Antiviral responses persisted at 12 hpi, accompanied by suppression of metabolic and translational processes, indicating a shift in host cellular priorities. By 18 hpi, metabolic reprogramming—particularly involving lipid and sphingolipid metabolism—was observed alongside altered immune signaling, consistent with viral exploitation of host cellular machinery. At 24 hpi, repression of genes involved in chromatin organization, RNA processing, spliceosome assembly, and ribosome biogenesis reflected a global transcriptional shutdown associated with cytopathic effects. Integration of temporal transcriptomic signatures enabled identification of host pathways amenable to pharmacological targeting. Selected host-directed compounds were evaluated in vitro and exhibited antiviral activity against CHPV in a neuronal cell line. Collectively, this study provides the first time-resolved transcriptomic landscape of CHPV infection in human cells and identifies host-targeted strategies relevant for antiviral development. Full article

The rapid expansion of the golden jackal (Canis aureus) across Eastern Europe has reshaped mesocarnivore communities, with potential influence on the dynamics of zoonotic disease. In Romania, where both Trichinella spp. and rabies remain public health concerns, updated data on wildlife reservoirs are essential. This study aims to provide an integrated assessment of Trichinella prevalence and rabies virus-neutralising antibody (RVNA) profiles in 134 wild canids (96 golden jackals and 38 red foxes, Vulpes vulpes) from northwestern Romania (August 2025–January 2026). Trichinella larvae were detected using the artificial digestion method, and infection intensity was expressed as larvae per gram. Rabies serology was performed using a commercial ELISA kit, with 0.5 IU/mL considered the protective threshold. Trichinella prevalence was significantly higher in foxes (78.9%) in comparison with jackals (60.4%), with similar larval burdens in both species. More than half of the individuals in both species exhibited RVNA titers below the protective threshold, indicating heterogeneous immunity levels in the population. No significant age- or sex-related differences in seroconversion were observed. These findings confirm intense sylvatic circulation of Trichinella spp. and highlight potential immunity gaps in wildlife rabies control. The results support the need for integrated, multi-pathogen surveillance and explicit inclusion of the golden jackal in disease monitoring and management strategies. Full article

Background: This case report presents a 12-year-old male with vertically transmitted chronic hepatitis B virus (HBV) infection, exhibiting a rare pan-reactive serological profile (concurrent HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb positivity) alongside fluctuating low-level viremia (HBV DNA: 1.06 × 10² IU/mL to undetectable). Rigorous exclusion of technical artifacts confirmed the authenticity of this atypical serologic pattern, observed in <0.001% of the general population. Methods: Liver biopsy and immunohistochemical staining were performed to evaluate hepatic inflammation and fibrosis. HBV serological markers and viral load were quantified using commercial diagnostic kits, with longitudinal monitoring for 18 months. Results: Liver biopsy revealed Grade 2 inflammation with focal HBsAg/HBcAg expression, supporting immune-active chronic hepatitis B (CHB) despite partial seroconversion. The patient’s clinical course highlights key challenges in pediatric HBV management: (1) delayed immune reconstitution (18-month longitudinal HBeAg/HBeAb dynamics), (2) non-linear virologic-ALT correlation, and (3) diagnostic ambiguity in pan-positive serology—potentially reflecting S-gene escape mutants or transitional immune responses. Initiation of tenofovir disoproxil fumarate (TDF) achieved sustained virologic suppression, underscoring the importance of early antiviral therapy in pediatric CHB with atypical markers. Conclusions: This case provides preliminary insights into the complex interplay between viral evolution and immature host immunity, advocating for refined monitoring protocols integrating high-sensitivity HBV DNA, quantitative serology, and non-invasive fibrosis assessment in pediatric HBV care. Full article

Understanding host cell response to viral infection could lead to the identification of molecular targets that can be used for the development of diagnostics and therapeutics. In this study, we investigated human dendritic cell (DC) response to infections with Vaccinia (VAC) virus, a highly immunogenic poxvirus, and Venezuelan Equine Encephalitis (VEE) virus, a single-stranded positive-strand RNA alphavirus, using human gene expression microarrays. Comparative changes in DC mRNA expression resulting from infection by the two viruses at 1, 8, and 12 h post-infection (hpi) revealed distinct temporal dynamics. VAC infection triggered early and robust activation of pathways related to chromatin organization, DNA damage, and antigen presentation, while VEE infection exhibited delayed activation of immune signaling pathways, including interferon signaling and cytokine production. Shared pathways, such as interferon signaling and inflammasome activation, highlight universal antiviral responses and potential therapeutic targets. These findings provide a molecular framework affected by VAC and VEE that need to be validated with additional experiments, such as functional assays or in vivo studies. The specific up- or downregulation of these pathways at different time points likely dictates the overall outcome of the viral infection and could potentially lead to better understanding of the temporal regulatory dynamics of virus host response. Full article

Epstein–Barr virus (EBV) establishes lifelong infection in most humans, yet its biology in immunocompetent hosts is commonly framed as a binary alternation between latency and productive lytic replication. Accumulating molecular and single-cell evidence challenges this view, indicating that EBV frequently enters abortive forms of lytic reactivation that do not culminate in virion production. Here, we propose a conceptual framework in which EBV persistence is governed by feedback-regulated interactions and permissive conditions for reactivation rather than a strictly sequential life cycle. Immediate-early and early gene expression can be repeatedly induced by inflammatory signaling, cellular stress, and epigenetic changes. However, progression to viral DNA replication represents a highly functional barrier that likely requires the coordinated convergence of multiple viral and host conditions. Failure to reach this threshold arrests reactivation before late gene expression, generating a stable partial lytic state characterized by sustained immunomodulatory viral protein expression without the production of infectious particles. Immune surveillance reinforces this bottleneck by eliminating cells undergoing full lytic replication while sparing those stalled in early phases. We argue that EBV persistence reflects a dynamic equilibrium shaped by regulatory interactions between viral gene expression and host immunity, with implications for biomarker interpretation and therapeutic strategies in chronic inflammatory and autoimmune disease. Full article

The eukaryotic translation initiation factor 4E (eIF4E) family plays a dual role in plants, regulating cap-dependent protein synthesis and mediating susceptibility to viruses in the family Potyviridae. In cowpea (Vigna unguiculata (L.) Walp.), an economically important legume cultivated worldwide, the structural determinants of these isoforms remain largely unexplored. This study characterizes the genomic organization, evolutionary history, and conformational dynamics of eIF4E, eIF(iso)4E, and nCBP in cowpea using a multi-omics approach. Genome mining identified three paralogous genes located on chromosomes 4, 6, and 7, showing high synteny with Phaseolus vulgaris. Phylogenetic analysis confirmed nCBP as the ancestral Class I lineage, distinct from the Class II eIF4E and eIF(iso)4E clades. Theoretical models for the isoforms were generated and subsequently validated by molecular dynamics simulations, revealing that while all isoforms preserve the canonical tertiary architecture and an electropositive cap-binding pocket, eIF(iso)4E exhibits superior structural compactness and hydrogen-bond stability. These biophysical features highlight their role as a stable anchor for viral VPg proteins. By elucidating the atomic-level landscape of these factors, we provide a robust structural framework to guide allele mining and genome-editing strategies aiming to engineer virus-resistant cowpea cultivars without compromising agronomic performance. Full article

Background/Objectives: Until now, there have been no suitable medicines to treat infections caused by the Ebola virus. Cistus incanus, a traditional medicinal plant, contains several phytocompounds exhibiting antioxidant and anti-inflammatory properties. Methods: In this research, the molecular level interactions of the phytocompounds of Cistus incanus were investigated for their antiviral potential against the active site of VP40 protein of Ebola virus using in silico molecular docking. Further, the potential compounds were assessed for their stability in the protein using molecular dynamics (MD) simulations. Results: Methyl gallate, catechin, and quercetin showed excellent docking scores of −9.8, −8.8, and −7.7 kcal/mol, respectively, and favorable interactions with the target protein. These complexes showed good stability over the 100 ns MD simulation time. In addition, the phytocompounds displayed favorable pharmacokinetics and drug-like properties. Conclusions: Our study offers the antiviral potential of phytocompounds (methyl gallate, catechin, and quercetin) of Cistus incanus, suggesting their suitability as lead candidates for the treatment of Ebola viral infection. Full article

Host receptors can detect traces of non-self-pathogenic RNAs within a sea of cellular mRNA molecules. In host cells, mRNA cap methylation occurs in the nucleus, generating Cap1 and Cap2 structures (m⁷GpppNm and m⁷GpppNmNm, respectively). By contrast, alphavirus genomes carry a Cap0 structure (m⁷GpppN), which lacks 2′-O-methylation. This difference in the structure of the host and viral caps serves as a molecular signature that enables discrimination between self and non-self RNAs. Several host immune sensors, such as RIG-I and IFIT1, recognize the alphavirus Cap0 structure and trigger an antiviral response to restrict viral replication. It has been proposed that IFIT1 sequesters aberrant RNAs, preventing their translation by host ribosomes and blocking viral protein synthesis. However, alphaviruses have evolved molecular strategies to circumvent IFIT1-mediated restriction and facilitate infection in mammalian cells. One such strategy involves the folding of a 5′ RNA structure that hides the cap from host immune sensors. This highlights the dynamic interplay between viral evasion tactics and host immune defenses. This review will discuss how specific modifications at the 5′ end of alphavirus RNA modulate host defenses and how a deeper understanding of the virus–host interaction may inform the development of novel vaccine strategies. Full article