Search Results (13,507)

Background: Hantavirus pulmonary syndrome (HPS), also designated hantavirus cardiopulmonary syndrome, is caused by New World hantaviruses, principally Sin Nombre virus in North America and Andes virus in South America. The syndrome is characterized by rapidly progressive noncardiogenic pulmonary edema and myocardial depression, with case fatality rates of 25% to 40%. A 2026 outbreak aboard an expedition cruise ship in the South Atlantic, comprising 13 cases and three deaths, confirmed that Andes virus can be transmitted between humans in a confined setting remote from the rodent reservoir. Methods: Virological, pathophysiological, clinical, and therapeutic aspects of HPS were reviewed, with particular emphasis on cardiopulmonary mechanisms. Sources were identified through PubMed, Scopus, and Google Scholar, with priority given to original research articles, clinical series, and controlled trials published through 2025. Literature published in English and Spanish was included. Results: Pathogenic hantaviruses enter endothelial cells and platelets via αvβ3 integrins, disrupting the VEGF-VEGFR2 signaling axis and rendering endothelial cells hypersensitive to physiological VEGF concentrations. Expansion of CD8+ T cells and activated macrophages releases TNF-alpha, IFN-gamma, and nitric oxide, amplifying microvascular permeability and contributing to myocardial depression. Autopsy studies demonstrate direct hantaviral myocarditis with viral antigen in cardiac endothelium and interstitial macrophages. Transpulmonary thermodilution confirms simultaneous hypovolemia, reduced global ejection fraction, and elevated extravascular lung water. Because the incubation period is long and the cardiopulmonary phase is substantially immune-mediated, seroconversion precedes rather than follows clinical deterioration, which preserves the diagnostic utility of IgM serology in a disease that can kill within 48 h. VA-ECMO initiated at the first signs of cardiopulmonary decompensation has reported survival rates approaching 80% in selected experienced centers. No antiviral has demonstrated efficacy in controlled trials during the cardiopulmonary phase, and no licensed vaccine exists. Conclusions: HPS produces a mixed shock state through increased microvascular permeability, T cell-mediated immunopathology, and direct myocarditis. Management follows a stepwise algorithm: suspected HPS triggers immediate complete blood count with peripheral blood smear and concurrent hantavirus IgM serology and RT-PCR, followed by ICU admission, conservative fluid resuscitation guided by transpulmonary thermodilution, and early contact with an ECMO-capable center at the first sign of rising lactate, falling cardiac index, refractory shock, arrhythmia, or rapid oxygenation failure. Full article

A lifelong career devoted to the development of specific antiviral agents eventually yielded, besides (almost) 3000 publications, about ten antiviral compounds that were approved and marketed as antiviral drugs, i.e., DHPA (Duviragel^®), BVDU (Zostex^®, Mevir^®, Brivir^®…), VACV (Zelitrex^®, Valtrex^®), d4T (Stavudine^®), emivirine (Coactinon^®), rilpivirine (Edurant^®), HPMPC (Vistide^®), PMEA (Hepsera^®), tenofovir (Viread^®) and AMD-3100 (Mozobil^®), with the latter as a hematopoietic stem cell mobilizer. The targeted viruses for these compounds were herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), human immunodeficiency virus (HIV), and hepatitis B virus (HBV). For other viruses, such as filo-, rhabdo-, arena-, myxo-, polyoma- and papillomaviruses, strategies have been elaborated that should facilitate future developments of antiviral drugs. Full article

Highly pathogenic RNA viruses, such as Ebola, SARS-CoV-2, and influenza, cause severe disease in humans. High mutation rates, which enable RNA viruses to evade immunity and escape antivirals, and their ability to spread from animals to humans and cause pandemics and outbreaks, make RNA viruses significant threats to public health. Diseases caused by Ebola, SARS-CoV-2, and influenza are prevented and treated with only a limited number of approved antiviral drugs, the effectiveness of which is limited by mutations in the viral targets. It is crucial to understand the structural determinants, molecular mechanisms, and host interactions of pathogenic RNA viruses to develop effective antiviral strategies. In this review, we discuss selected RNA viruses, focusing on the structure of their RNA polymerases and interactions with host factors during the different stages of the viral lifecycle, as well as the traditional antivirals targeting these structures and pathways. Furthermore, emerging concepts such as liquid–liquid phase separation and biomolecular condensates, and novel promising antiviral strategies are discussed. Understanding shared and distinct structures, molecular mechanisms, and host interactions across highly pathogenic RNA viruses enables the discovery of new and more effective antiviral strategies, ultimately improving clinical outcomes against evolving RNA viruses. Full article

Direct-acting antivirals (DAAs) cure most chronic hepatitis C virus (HCV) infections, yet whether the gut microbiota returns toward a healthy state after viral clearance remains uncertain. We systematically reviewed DAA-era adult HCV studies using sequencing-based fecal microbiota assessment (PROSPERO CRD420261374682). Longitudinal alpha-diversity change was pooled by REML random-effects meta-analysis with Hartung–Knapp adjustment, and compositional/functional findings were synthesized narratively. Seven studies met qualitative criteria and five longitudinal reports were extractable. Because participant overlap between two Thai reports could not be excluded, the primary conservative non-overlap analysis of four reports (180 paired observations) gave Hedges’ g = 0.13 (95% CI −0.53 to 0.80; I² ≈ 89%); the five-report sensitivity estimate was directionally positive but imprecise (g = 0.35, 95% CI −0.38 to 1.07). Recovery concentrated in richness (Chao1), whereas evenness-weighted diversity (Shannon, Hill) barely moved; beneficial taxa such as Faecalibacterium and Blautia increased after SVR. These findings are consistent with uneven, richness-led microbial recovery, but the overall certainty of the pooled evidence is very low (GRADE); functional and clinical recovery remain insufficiently characterized and undemonstrated. Full article

Maraviroc (MVC), a CCR5 antagonist, has been proposed as a potential antiviral agent against SARS-CoV-2; however, its mechanism of action across viral variants remains unclear. Here, we evaluated the antiviral activity of MVC against SARS-CoV-2 wild-type (WT) and Omicron BA.1 variants using single-round infectious particles (SRIPs), virus-like particles (VLPs), and cell-based assays, with a focus on its impact on viral entry and Mpro function. MVC potently inhibited infection of both WT and BA.1 SRIPs in Vero E6 cells, exhibiting EC₅₀ values of 0.0065 μM and 0.016 μM, respectively. Time-of-addition assays revealed that MVC primarily targets the early phase of infection, with the strongest inhibition observed at the viral entry stage, while moderate effects were detected during attachment and post-entry stages. Fluorescence-labeled VLP imaging demonstrated distinct entry pathways, with WT predominantly entering via plasma membrane fusion and BA.1 via endocytosis, independent of cell type. MVC altered WT-VLP trafficking by promoting internalization and lysosomal localization, whereas it had minimal impact on BA.1 internalization. In spike-mediated cell–cell fusion assays, MVC preferentially inhibited WT spike-driven syncytium formation but showed limited effects on BA.1 or BA.4 fusion, while more effectively reducing Omicron spike-mediated binding. At the post-entry stage, MVC inhibited SARS-CoV-2 main protease (Mpro) activity, with BA.1 Mpro (P132H) exhibiting greater sensitivity (IC₅₀ = 0.496 µM) than WT (1.869 µM). Collectively, these findings demonstrate that MVC exerts variant-dependent antiviral effects by targeting viral entry, modulating trafficking pathways, and inhibiting Mpro activity. This study highlights MVC as a multi-stage inhibitor with differential efficacy against SARS-CoV-2 variants, providing insights into its potential therapeutic application. Full article

5′-Adenosine monophosphate-activated protein kinase (AMPK) is the principal cellular energy sensor that coordinates metabolic adaptation by balancing anabolic and catabolic pathways in response to energic stress. Beyond its canonical role in maintaining energy homeostasis, AMPK has emerged as a central regulator of host–pathogen interactions by integrating lipid metabolism, autophagy, mitochondrial dynamics, oxidative stress, and innate immune signaling. Flaviviruses, including dengue virus, Zika virus, West Nile virus, Japanese encephalitis virus, and yellow fever virus, extensively remodel host metabolism to establish productive infection. As a master regulator of cellular metabolism, AMPK can either restrict or facilitate flavivirus replication in a context-dependent manner by regulating lipid droplet biogenesis, fatty acid synthesis and beta-oxidation, autophagy, mitochondrial homeostasis, and interferon-mediated antiviral responses. Conversely, flaviviruses actively manipulate AMPK signaling and its downstream metabolic networks to promote endoplasmic reticulum remodeling, replication organelle biogenesis, energy production, and immune evasion. In this review, we summarize recent advances in understanding the multifaceted roles of AMPK during flavivirus infection, with an emphasis on its regulation of metabolic reprogramming, organelle remodeling, and antiviral immunity. We further discuss the therapeutic potential of pharmacologically targeting AMPK and its downstream pathways as a host-directed strategy for broad-spectrum antiviral intervention against flaviviruses. Full article

Autophagy is a conserved cellular degradation pathway that plays important roles in insect–virus interactions. In the MED cryptic species of Bemisia tabaci, cotton leaf curl Multan virus (CLCuMuV) can persist upon acquisition, yet this vector fails to transmit the virus. However, whether autophagy contributes to this antiviral response in MED whiteflies remains unknown. In this study, we show that CLCuMuV acquisition activates autophagy in MED whiteflies, as evidenced by increased LC3-I to LC3-II conversion, enhanced LC3-positive puncta formation in the gut, and dynamic transcriptional regulation of multiple autophagy-related genes. Functional investigations using RNAi-mediated silencing of Atg3 and Atg9, two essential autophagy genes, revealed that their knockdown elevated viral DNA accumulation by 1.4-fold at 48 h post-acquisition. Consistently, pharmacological blockade of autophagic flux with bafilomycin A1 led to a 1.0-, 2.2-, and 1.0-fold increase in viral loads across 24, 48, and 72 h post-acquisition, respectively, whereas treatment with rapamycin, an autophagy inducer, decreased viral DNA accumulation by 46.4% and 33.3% relative to control levels at 24 and 48 h post-acquisition, respectively. Together, these loss- and gain-of-function experiments demonstrate that autophagy functions as a host restriction mechanism that limits CLCuMuV persistence in MED whiteflies, providing molecular insights into the immune competence of this non-vector species. Full article

Infectious bovine rhinotracheitis virus (IBRV) causes highly contagious bovine respiratory disease and threatens the global cattle industry. Ferroptosis, an iron-dependent regulated cell death, is involved in multiple viral infections, but its role and mechanism in IBRV infection remain unclear. This study investigated IBRV-induced ferroptosis and the NFKB1-SLC39A8 axis in MDBK cells and examined the effect of ferroptosis on IBRV replication. Ferroptotic phenotypes and molecules were detected by biochemical assays, qPCR, Western blotting and TEM. Gain- and loss-of-function assays were performed to modulate gene expression, and their transcriptional relationship was verified by dual-luciferase assay. IBRV induced typical ferroptosis in MDBK cells, including Fe²⁺ overload, excessive ROS and MDA accumulation, GSH depletion and mitochondrial damage. Ferrostatin-1 reversed these changes and reduced viral titers, suggesting that ferroptosis contributes to IBRV replication. SLC39A8 overexpression aggravated ferroptosis, whereas its knockdown suppressed it. Mechanistically, our data support that NFKB1 positively regulates SLC39A8 transcription, and NFKB1 silencing inhibited IBRV-induced ferroptosis. In conclusion, this in vitro study shows that IBRV induces ferroptosis in MDBK cells via the NFKB1-SLC39A8 axis, and ferroptosis may contribute to viral replication. These findings provide insights into IBRV–host cellular interaction and identify potential candidate molecular targets for future antiviral research. Full article

The biosynthesis of copper and copper oxide nanoparticles (Cu/CuO-NPs) has attracted considerable interest due to its non-toxic, eco-friendly nature and wide-ranging applications, especially in nanomedicine and biomedical fields. Traditional nanoparticle production methods often involve toxic chemicals and generate harmful byproducts. In contrast, biological synthesis provides a cleaner, safer, more cost-effective, and sustainable alternative. Various biological sources, including plants, bacteria, fungi, and yeast, have been employed for the efficient and non-toxic production of Cu/CuO-NPs. These organisms contain diverse biomolecules such as enzymes, proteins, amino acids, vitamins, flavonoids, and alkaloids that function as reducing, capping, and stabilizing agents during nanoparticle formation. The biologically synthesized Cu/CuO-NPs are characterized using UV-VIS spectroscopy, Raman spectroscopy, TEM, SEM, EDX, XRD, TGA, XPS, FTIR, DLS, zeta potential analyzer, etc. Cu/CuO-NPs hold promise for applications in nanomedicine, primarily because of their strong antimicrobial and anticancer activities and potential use as disinfectants against infectious diseases. Various reports have suggested that the biologically synthesized Cu/CuO-NPs have exhibited significant antimicrobial and anticancer efficacies against pathogenic bacteria, fungi and viruses and various cancer cells. Due to their nanoscale dimensions and extensive surface area, Cu/CuO nanoparticles can readily infiltrate cell walls, disrupt membrane integrity, generate reactive oxygen species, and hinder both DNA replication and protein production, leading to cell death. The present review comprehensively describes the biological synthesis of Cu/CuO-NPs, their characterization techniques, and potential antibacterial, antifungal, antiviral, and anticancer applications. The modes of action for antibacterial, antifungal, antiviral, and anticancer properties have also been explored critically. Full article

Essential oils derived from plants have gained increasing interest in recent years for their potential antimicrobial, antiviral, and disinfectant properties. However, data specifically examining the virucidal efficacy of essential oils against human papillomavirus (HPV), a major human pathogen, remains very limited. In this study, we compared the chemical composition of sandalwood essential oils derived from five different species (Santalum album, S. austrocaledonicum, S. insulare, S. paniculatum, and S. spicatum). We further investigated the ability of S. album sandalwood oil, the species highest in α- and β-santalol content, to inactivate infectious HPV type 16 virions dried onto glass carriers at contact times of 5 and 30 min. HPV-16 is a high-risk HPV type frequently associated with cervical and other cancers. A RT-qPCR assay based on E1^E4 spliced transcript detection was used to measure viral infectivity levels post-treatment. S. album oil exhibited moderate but incomplete virucidal activity, achieving a mean 2.59 log reduction (99.7% inactivation) of HPV-16 after a 30 min contact time. In contrast, the shorter 5 min contact time resulted in negligible reductions in viral infectivity compared to untreated controls. These data suggest that while S. album oil has the ability to inactivate HPV, it requires relatively long contact times to achieve significant reduction. Full article

SARS-CoV-2 relies on a virus-encoded RNA capping pathway to produce 5′ cap structures that are essential for mRNA stability, efficient translation, and evasion of host innate immune surveillance. Within this pathway, nonstructural protein 14 (nsp14) catalyzes N7 methylation of the guanine cap, a key step that converts the cap core into a functional Cap-0 structure and enables subsequent maturation. Owing to its essential role in viral replication and its high conservation across coronaviruses, nsp14 has emerged as an attractive antiviral target. Recent structural and biochemical studies have elucidated the architecture of the nsp14 N7-methyltransferase domain, revealing an S-adenosyl-L-methionine (SAM)-dependent fold with a defined cofactor-binding site and an adjacent cap-binding pocket that orients the RNA substrate for methyl transfer. These insights have guided the development of diverse inhibitor classes, including SAM-competitive analogs, bisubstrate-like compounds, and non-nucleoside inhibitors identified through screening approaches. While early SAM-like inhibitors demonstrated target tractability, their therapeutic potential has been limited by challenges in selectivity and cellular permeability. More recent inhibitors that target the cap-binding pocket or exploit product-assisted ternary complex mechanisms highlight alternative strategies for achieving improved potency and specificity. Despite these advances, current structural models rely on truncated RNA substrates and isolated protein constructs, which may not fully capture the native catalytic environment. Future efforts to resolve nsp14 within the replication–transcription complex and develop novel inhibition strategies will be critical for advancing mechanistic understanding and antiviral development. Full article

Rose rosette virus (RRV) causes witches’ broom disease in roses. This study examined whether differences in disease in these spatially distinct domains are associated with local changes in defense-related hormones and transcriptional reprogramming. The levels of defense-related phytohormones salicylic acid (SA), jasmonic acid (JA), 9-lipoxygenase (9-LOX), 13-lipoxygenase (13-LOX), and derived oxylipins were different in these distinct tissues. We curated differentially expressed genes involved in the biosynthesis, storage, and signaling of SA, JA, and oxylipins to reveal how specific defense pathways correlate with these distinct disease states. Gene ontology (GO) analysis and the Disease Resistance Analysis and Gene Orthology 3 (DRAGO3) pipeline revealed stress-associated genes and classical resistance (R) gene families that were differently expressed in these distinct tissue domains. Promoter analysis of defense-associated transcription factors and histone modifiers revealed hormone responsive elements, suggesting complex hormone crosstalk is involved in defense-related gene expression. We confirmed by RT-qPCR, a notable subset of defense genes in the chromosome 5 hotspot, specifically in the linkage group 5 (LG5) quantitative trait loci, linked to reduced RRV susceptibility, was altered in both field-infected and greenhouse-inoculated plants. The association of high versus low disease states with distinct defense hormone signatures and gene expression patterns suggests that local immune states, rather than whole-plant defenses, determine whether a cane becomes rosetted or remains asymptomatic. Full article

Background and Clinical Significance: Eczema herpeticum (EH), or Kaposi’s varicelliform eruption, is a dermatologic emergency characterized by the abrupt onset of painful monomorphic vesiculopustules with potential for rapid dissemination. Atopic dermatitis (AD) is the main predisposing condition due to skin barrier dysfunction and impaired antiviral immunity. Early recognition is essential because delayed treatment may result in avoidable complications, including ocular involvement and systemic disease. Current recommendations emphasize immediate systemic acyclovir based on clinical suspicion, without awaiting laboratory confirmation. Case Presentation: A 4-year-old boy with moderate AD presented with a 6-day history of fever, malaise, and a rapidly progressive vesiculopustular eruption involving both eczematous and previously unaffected skin. The patient had a recent AD flare, molluscum contagiosum, and had initially received oral amoxicillin-clavulanate for presumed bacterial superinfection without improvement. Physical examination revealed widespread painful monomorphic umbilicated vesiculopustules with hemorrhagic crusts and mild bilateral conjunctival injection. Oral acyclovir was initiated within one hour of evaluation. Laboratory investigations showed mild inflammatory abnormalities without renal or hepatic involvement. Because lesional PCR was unavailable, complementary blood-based investigations were performed; HSV-1 IgM serology and blood PCR provided additional retrospective findings compatible with HSV-1 infection, while Gram stain and bacterial cultures were negative. Fever resolved within 24 h, no new lesions developed after day 3, and complete re-epithelialization was achieved after a 10-day course of acyclovir. Conclusions: This case highlights the importance of bedside recognition of eczema herpeticum in children with atopic dermatitis, particularly when painful monomorphic vesiculopustules are accompanied by fever and rapid dissemination. Early initiation of systemic acyclovir based on clinical suspicion remains the cornerstone of management. While PCR from vesicular lesions is the preferred diagnostic test when available, laboratory confirmation should not delay treatment. This report also illustrates common real-world challenges, including initial misdiagnosis as bacterial infection and limited access to optimal virological testing. Full article

The porcine interferon (IFN) system is highly diversified, particularly within Type I subfamilies, yet its evolutionary trajectory across domestication and breed formation remains poorly characterized. We performed a comprehensive comparative genomic and structural analysis of 432 IFN sequences spanning all IFN types across 11 Sus scrofa breeds representing commercial, indigenous, and wild/outgroup lineages. Phylogenetic reconstruction, pairwise dN/dS selection pressure analysis, and AlphaFold2-based 3D structure prediction coupled with DALI structural similarity mapping were integrated to resolve repertoire architecture, evolutionary constraints, and domestication-associated divergence. IFN repertoire organization is governed primarily by family identity rather than breed origin, with Type I IFN-α, -δ, and -ω subfamilies showing pronounced gene expansion in domestic breeds. Phylogenetic clustering and structural similarity consistently grouped sequences by subtype, independent of domestication history. Pervasive purifying selection (median ω = 0.48) maintained functional constraints across all lineages. Commercial breeds exhibited significantly higher within-category structural convergence alongside expanded repertoires, while structural conservation was evolutionarily decoupled from sequence-level selective pressure. Domestication potentially drove coordinated IFN repertoire expansion and structural conservation with related purifying selection at the gene level. These findings establish a genomic framework linking breed-specific IFN architecture to antiviral capacity and provide a foundation for immunogenetic-informed breeding strategies in the swine model. Full article

The emergence of SARS-CoV-2 variants and antiviral resistance highlights the need for improved therapeutic strategies against COVID-19 and other coronavirus infections. By pairing direct-acting antivirals with repurposed host-modulating drugs, combination therapy approaches may enhance antiviral efficacy while mitigating inflammation. In this study, we evaluated the effects of combining Nirmatrelvir (a SARS-CoV-2 main protease inhibitor) with Ivermectin, Azithromycin or Doxycycline—using a murine hepatitis virus (MHV) infection model of RAW264.7 macrophages. Checkerboard assays demonstrated that the Nirmatrelvir–Ivermectin combination exhibited strongly synergistic antiviral activity. This combination achieved potent inhibition of live virus titer of at least 5 to 6 log₁₀ and reduction in viral RNA load of 3 log₁₀, at drug concentrations much lower than the respective monotherapies. The Nirmatrelvir–Ivermectin combination treatment affected the coronavirus replication cycle at the same time-point of 8 h as Nirmatrelvir monotherapy. Moreover, multiplex cytokine protein profiling revealed that Nirmatrelvir–Ivermectin markedly suppressed key pro-inflammatory cytokines and chemokines associated with the cytokine storm, including IL-6, TNF-α, IL-1β, and MCP-1. Conversely, the combinations of Nirmatrelvir with Azithromycin or Doxycycline exhibited only additive or mildly additive effects, with alterations in certain cytokine levels. These findings support the potential of Nirmatrelvir–Ivermectin as a promising novel combination therapy with both antiviral and anti-inflammatory benefits, warranting further in vivo validation and clinical investigation. Full article