Lipid-mediated broad-spectrum antiviral mechanism of alpha-linolenic acid against respiratory enveloped viruses.

XBP1 and ATF4 inhibit WSSV replication and promote host survival by modulating Spatzle expression in Macrobrachium nipponense.

It is widely known that numerous enveloped viruses can produce multinucleated cells (syncytia) as a result of viral entry-related membrane fusion events. By protecting the virus from the host's immune reaction, these syncytia are thought to promote viral reproduction. Syncytia are collections of merged cells. A viral spike protein (S) on the surface of an infected cell interacts with receptors on nearby cells to cause the syncytia response. The innate immune system's response to viruses affects how syncytia form. Some interferon-stimulated genes change the membrane in a way that reduces the likelihood of fusion. The severe acute respiratory syndrome coronavirus (SARS-CoV-2) virus is quickly changing; also, several mutations occurred in its S protein. Individually and together, the Alpha, Beta, Gamma, and Delta variants carry mutations that significantly affect S function and syncytia formation. The function of syncytia in newly emerging variant diseases is still unknown, though. Syncytia could cause disease through promoting viral transmission, cytopathicity, immunological evasion, and inflammatory responses. The SARS-CoV-2 S protein variations include several changes that improve receptor interactions, fusogenicity, and antibody reactivity. A wide range of clinical symptoms, including moderate febrile sickness, severe respiratory distress, and occasionally deadly lung damage, can be brought on by an infection with SARS-CoV-2. Several of these lung illnesses (MERS-CoV) are linked to both the Middle East Respiratory Syndrome (MERS) and the severe acute respiratory syndrome coronavirus (SARS-CoV). Compared to acute respiratory syndromes, the lung thrombosis brought on by Coronavirus disease 2019 (COVID-19) is incredibly severe. In this review we focused on innate immunological elements that prevent syncytia from forming and the molecular triggers of S-mediated fusion.

Fe2O3-based nanozyme synergistic with oseltamivir for broad-spectrum inhibition of influenza A virus.

Targeting dengue virus envelope protein: Insights from structural analysis and high-throughput screening.

Lauric Acid (LA) and Glycerol Monolaurate (GML) are naturally present in several plant-derived oils, particularly coconut and palm kernel oil. These compounds have been widely applied in swine production owing to their proven antiviral activity against Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), Porcine Epidemic Diarrhoea Virus (PEDV), and African Swine Fever Virus (ASFV). In this study, we investigated the potential of LA and GML as antiviral agents against Cyprinid herpesvirus 2 (CyHV-2), the causative agent of Herpesviral haematopoietic necrosis (HVHN), which poses significant challenges to China's freshwater aquaculture industry, particularly in crucian carp farming. Notably, no commercially available drugs or vaccines are currently approved for CyHV-2 infection. Our findings demonstrated that LA and GML significantly inhibit CyHV-2 replication and reduce viral infectivity. Further investigation into the antiviral mechanisms revealed that treatment with LA or GML disrupts the viral envelope structure, alters its physicochemical properties, and compromises virions' stability. Based on these results, we propose that LA and GML are promising natural antiviral agents for the control of CyHV-2 infection.

Dengue fever is one of the most widely distributed vector-borne infectious diseases globally, prevalent in tropical and subtropical regions. An estimated 3.9 billion people in 128 countries are at risk of infection globally, and the 2024 outbreak was the most severe. As a tropical region, Hainan Province in China serves as a significant endemic area for dengue fever, where epidemic prevention and control remain critical. To analyze the transmission dynamics and pathogen variation characteristics of the 2024 dengue fever outbreak in Hainan Province. Acute-phase serum samples from 18 confirmed dengue cases during the 2024 outbreak in Hainan Province were collected and serotyped using TaqMan real-time PCR. The viral envelope (E) gene and representative whole genomes were sequenced and compared with domestic reference strains to assess epidemic trends. Phylogenetic and molecular clock analyses were performed based on E gene and full-genome sequences to infer spatiotemporal transmission dynamics. Sequence alignment and homology modeling were used to identify E gene mutations and evaluate their potential effects on E protein functional domains and viral pathogenicity. Among the 18 samples, 17 were dengue virus (DENV)-1, and 1 was DENV-3. Phylogenetic analysis revealed that the primary strains in this outbreak were highly homologous to those circulating in Guangdong Province; however, two strains exhibited significant genetic differences, suggesting possible independent introduction. Additionally, two unique DENV-1 E gene mutations (D147N and S338L) were identified, which we hypothesize may be associated with viral characteristics, subject to further functional verification. This study systematically reveals the epidemiological characteristics of the 2024 dengue fever outbreak and provides a scientific basis for formulating local control strategies and a research foundation for further exploring the molecular-level pathogenicity and transmissibility of DENV.

Virucidal multipurpose aqueous solution containing quaternary ammonium cation and sulfobetaine is effective against highly pathogenic avian influenza viruses.

LTX-109 as a broad-spectrum antiviral: in vitro and in vivo efficacy against SARS-CoV-2 and influenza viruses.

An aminopeptidase N homolog is associated with white spot syndrome virus infection susceptibility in Penaeus japonicus.

Multi-target inhibitors of white spot syndrome virus envelope proteins (VP28, VP26, and VP24) to protect shrimp (Penaeus monodon): An integrated virtual screening, pharmacokinetic, and molecular dynamics study.

Germinal centers (GCs) are a complex and important aspect of humoral immunity. How GCs deal with changing antigens remains unclear, yet this biology could be central to next-generation vaccine strategies such as germline targeting. Here we demonstrate, in a mouse model with human immunodeficiency virus envelope surface protein immunogens, that rapid delivery of homologous or heterologous boosts results in highly positive outcomes. Rapid reimmunization expands on-target GC B cell (BGC) populations, which emerge almost exclusively from existing BGC cells. Early homologous boosting avoids prohibitive antibody titers and utilizes off-target antibodies to maximize the BGC response. Heterologous rapid boosting shifts affinity maturation towards the new antigen. The 'refueled' GCs are sustained, developing large affinity gains and evolving rapidly to bind wildtype HIV Env trimer within 56 days, even when using as few as two distinct antigens. These findings provide insights into GC biology and translatable paths to leveraging accelerated GC function.

Extracellular release of cytotoxic aggregates by HSV-1-replicating SH-SY5Y cells: involvement of alpha-synuclein and poly-ubiquitin conjugates.

Jaagsiekte sheep retrovirus (JSRV) causes ovine pulmonary adenocarcinoma (OPA), and its pathogenesis is primarily mediated by the viral envelope (Env) protein. However, the detailed oncogenic mechanisms underlying JSRV infection remain incompletely understood. In this study, we integrated transcriptomic and metabolomic analyses to characterize JSRV Env-induced alterations in human bronchial epithelial BEAS-2B (cells). BEAS-2B cells transfected with the pcDNA4.0myc-his-JSRV-env plasmid, those transfected with the empty pcDNA4.0myc-his vector, and untreated BEAS-2B cells served as the experimental, negative control, and blank control groups, respectively. Transcriptomic analysis identified a total of 2733 differentially expressed genes (DEGs). Specifically, relative to the blank and negative control groups, 1178 genes were upregulated and 307 were downregulated in the JSRV-env group. These DEGs were significantly enriched in pathways related to altered cellular energy metabolism, cell cycle regulation, and oncogenic signaling. Metabolomic analysis revealed 451 differentially expressed metabolites (DEMs), with 192 detected in positive ion mode and 259 in negative ion mode. Compared with both control groups, the JSRV-env group exhibited 33 upregulated and 46 downregulated DEMs in positive ion mode, as well as 22 upregulated and 55 downregulated DEMs in negative ion mode. These DEMs were significantly enriched in pathways such as cellular metabolism, purine metabolism, amino acid metabolism, and the tricarboxylic acid cycle. Notably, cellular and mitochondrial energy metabolism pathways were closely linked. Analyses of mitochondrial- and mitophagy-related genes, alongside an integrated transcriptomic and metabolomic evaluation of their interactions, suggested mitochondrial damage and the potential activation of mitophagy. Furthermore, JSRV Env-transformed BEAS-2B cells exhibited elevated reactive oxygen species, decreased mitochondrial membrane potential, and abnormal mitochondrial morphology-characterized by swelling, as well as fragmented, dissolved, or disappearing cristae-along with the presence of myelin-like mitochondrial lesions and mitophagosomes. Mitochondrial and lysosomal probe co-localization further confirmed mitochondrial degradation in the transformed cells. Overall, these results highlight the potential involvement of altered mitochondrial energy metabolism and mitophagy in JSRV Env-induced BEAS-2B cell transformation. These findings offer novel insights into the mechanisms of viral oncoproteins, cellular metabolic reprogramming, and mitophagy, while identifying potential targets for understanding JSRV pathogenesis.

Microplastics as Emerging Viral Vectors: Nexus, Mechanisms, Ecological Implications and Health Risks.

The bioactive constituents of ginger (Zingiber officinale Roscoe) display well-documented immunomodulatory and antimicrobial effects; however, the role of these components in combating dengue virus (DENV) and other flaviviruses infection remains unknown. Here, activity-guided molecular networking and antiviral screening identified 10-shogaol as the primary antiviral phytochemical in ginger, with a half-maximal inhibitory concentration (IC50) value of 2.502 μM. Mechanistically, 10-shogaol bound the n-octyl-β-d-glucopyranoside (β-OG) pocket of viral envelope protein (E), interfering with viral attachment and conferring broad antiviral properties against DENV and Zika virus (ZIKV). Additionally, 10-shogaol suppressed proinflammatory cytokines and mitigated tissue damage in mice by acting as a novel Nrf2 activator by inhibiting Keap1-mediated ubiquitination and proteasome degradation. Activation of Nrf2 by 10-shogaol induced antioxidant gene expression and inhibited inflammatory NF-κB signaling. Collectively, our study suggests that 10-shogaol acts as a broad-spectrum entry inhibitor against DENV and ZIKV as well as confers anti-inflammatory benefits for mitigating virus-induced inflammatory tissue damage.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assembles its viral envelope at the endoplasmic reticulum-Golgi intermediate compartment (ERGIC), yet the minimal molecular requirements for forming a stable viral envelope remain unclear. Here, we used coarse-grained molecular dynamics simulations to systematically examine how protein and lipid compositions and protein orientation influence membrane remodeling during viral envelope formation. Starting from bicelle membrane patches, we compared lipid-only systems and membranes containing the matrix (M) and spike (S) proteins under different lipid environments and orientations. Lipid-only membranes closed stochastically, whereas systems containing either M or S proteins reliably formed vesicles but failed to establish correct membrane topology. In contrast, systems containing both M and S proteins in heterogeneous ERGIC-like lipid mixtures consistently produced stable vesicles with correct topology. Mechanistic analyses revealed that protein orientation modulates membrane curvature generation and cholesterol redistribution, while persistent M-S contacts organize protein positioning during closure. Disrupting any of these interactions resulted in failed closure or severely deformed structures. Together, these results support an obligate-synergy model in which three interaction classes─M-S protein-protein contacts, M-lipid interactions, and S-lipid interactions─cooperate to drive robust coronavirus envelope assembly. These findings identify minimal physical requirements for viral envelope formation and provide mechanistic insights that may guide the rational design of coronavirus virus-like particle (VLP) assembly systems.

The manufacture of monoclonal antibody (mAb) therapeutics relies on stringent downstream processing, where low-pH viral inactivation (VIN) safeguards against enveloped viruses. Here we introduce simultaneous absorbance, polarized intrinsic emission, and scattering (APIES) measurements as a rapid (<1 min), robust analytical platform for real-time assessment of protein aggregation, concentration, and tertiary structural integrity during VIN. Dual excitation wavelengths (280 and 350 nm), multichannel detection, and parallel polarizers provide high sensitivity for aggregation monitoring. APIES provides three orthogonal readouts: protein concentration via A280, aggregation by an aggregation index (AggIndex = (A350/(A280 - A350)) × 100), Rayleigh-to-fluorescence ratios (IR/IF), and large tertiary structure changes (e.g., unfolding) via an intrinsic emission ratio (I350/I330). We evaluated APIES using a bovine IgG model (∼1 mg mL-1) undergoing simulated VIN at pH 3.4, 3.6, and 3.8 for 8 h. Measurements were acquired hourly using APIES, dynamic light scattering (DLS), and absorbance spectroscopy, with offline size exclusion chromatography (SEC) after sample neutralization. Under all pH conditions, DLS and APIES confirmed extensive increases of in-vessel aggregation, with AggIndex and IR/IF strongly correlating with DLS determined aggregate content (R2 > 0.9). However, SEC only showed an increase in irreversible aggregates (of ∼5% after 8 h) at pH 3.4, with no increase for pH 3.6 or 3.8. This highlights a limitation of SEC for in-process monitoring and shows that APIES better monitors in-vessel aggregation. Furthermore, APIES, via AggIndex and IR/IF ratio scatter plots, potentially distinguishes between reversible from irreversible aggregation pathways. Repeating these experiments using a flowcell over 3 h, with 1 min APIES measurement sampling intervals, confirmed that APIES was suitable for online aggregation monitoring. Overall, APIES is a simple, fast, and sensitive process analytical technology for real-time protein aggregation monitoring during industrial processes like VIN.

Dengue is an arboviral disease with major global public health impact. Its pathophysiology involves complex interactions between the virus and the host, including the immune response and the vascular endothelium. In this context, platelets play roles beyond hemostasis, acting as key immunomodulatory cells involved in inflammation and the regulation of vascular permeability. Therefore, this review summarizes and discusses the so called classic and non-classic platelet-related and endothelial biomarkers described in dengue virus infection. Classical biomarkers include P-selectin (CD62P), PF4/CXCL4, RANTES/CCL5, CD40L, IL-1β, VEGF, integrin αIIbβ3, CD63, and platelet extracellular vesicles, all supported by broad experimental and clinical evidence. Non-classical or emerging biomarkers include TLT-1, TREM-1/sTREM-1, angiopoietins (Ang-1/Ang-2), serotonin, ferritin, dengue virus envelope domain III (EIII), and soluble endothelial molecules such as IL-1RA, sCD163, SDC-1, sVCAM-1, IL-8, and IP-10. Alone or in combination, these markers can be used/explored as prognostic tools and/or as therapeutic targets. Finally, integrating multimarker panels encompassing hemostatic, inflammatory, and endothelial pathways may improve prognostic stratification. This approach could support targeted interventions and help reduce complications such as thrombocytopenia, plasma leakage, and dengue shock.

Morphological variability in virion size and shape (pleomorphism) is a prominent feature of many pathogenic enveloped viruses, but understanding its biology presents a long-standing challenge. Understanding the role of pleomorphism in viruses requires structural and functional analysis of virions across broad scales, from molecules and cells to animals and populations. The extent of our understanding of viral pleomorphism has hinged on technological advances in viral analysis of increasingly challenging samples, which now approach high-resolution measurements of viral dynamics in animal infections. We review progress in the field by describing both the foundational work and the ensuing characterization of influenza virus pleomorphism over eight decades and then reassessing it through an alternative lens. We argue that virion shape is not a fixed property of a viral strain but rather a dynamic characteristic that varies according to infection environment to improve viral fitness and facilitate persistence. We then describe pleomorphism in other viruses, particularly Mononegavirales, highlighting shared and unique features with influenza virus. We conclude by discussing emerging technological advances promising to answer unresolved questions about the biology of pleomorphism.