From the perspective of both the host cell and the virus, cholesterol (CHO) plays a critical role during viral infection. Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases the risk of cardiovascular disease by regulating plasma levels of lipoprotein(a), triglyceride-rich lipoproteins, and low-density lipoprotein cholesterol (LDL-C), and by promoting the degradation of the LDL receptor (LDLR). Emerging evidence implicates PCSK9 in the pathophysiology of several viral diseases, including human immunodeficiency virus (HIV), SARS-CoV-2, dengue virus (DENV), and hepatitis viruses. Two monoclonal antibody PCSK9 inhibitors (PCSK9i), evolocumab (Repatha®) and alirocumab (Praluent®), are approved by the Food and Drug Administration (FDA) for managing atherosclerotic risk. However, despite preclinical studies suggesting that these inhibitors and other CHO-lowering medications may interfere with viral replication, their therapeutic application as antivirals remains limited due to various restrictions. Naturally occurring compounds such as curcumin, berberine, quercetin, and polyphenols have demonstrated PCSK9-modulating and antiviral properties in preclinical models against viruses including HIV, hepatitis viruses, SARS-CoV-2, DENV, herpes simplex virus, human cytomegalovirus, and Epstein-Barr virus. Crucially, the majority of evidence for these natural substances remains preclinical, derived from in vitro and animal studies. The contribution of PCSK9 inhibition to the reported antiviral effects remains unclear, as pleiotropic mechanisms may be involved. Therefore, rather than being clinically proven substitutes for licensed PCSK9-targeted treatments, these molecules should be considered experimental or maybe supplementary medicines. This review examines the current preclinical evidence for natural inhibitors of PCSK9 and their antiviral properties, discusses clinical assessments to date, and considers the potential future role of naturally occurring PCSK9i in antiviral development, acknowledging the substantial research gaps that remain.
SUMMARYClass I fusion proteins are trimeric viral membrane proteins that mediate fusion between the virion and cellular membranes. In their prefusion state, they comprise three domains: a globular "head" domain that binds the target cell receptor, a helical "stalk" domain, and a transmembrane domain (TMD) at the carboxy-terminal end that anchors the protein in the viral membrane. However, it is now evident that the role of the TMD extends beyond simple membrane anchoring. This review explores the dynamic and regulatory functions of the TMD throughout the viral life cycle. TMDs contribute to intracellular trafficking and modulate membrane fusion activity and receptor binding. During virion assembly, they facilitate the incorporation of fusion proteins into budding particles, and influence virion formation and release. Furthermore, TMDs mediate interactions between viral and host proteins, shaping the structural organization of viral complexes, and impacting cellular responses to infection. Collectively, these findings highlight the TMD as a critical determinant of viral fitness and infectivity, underscoring its potential as a novel therapeutic target.
Mitochondrial antiviral signaling protein (MAVS) forms prion-like aggregates to activate innate immunity against RNA viruses, but the metabolic regulation of MAVS remains poorly understood. Here, we show that viral infection induces the formation of lipid droplets (LDs), which physically interact with mitochondria to promote the assembly of MAVS prion-like aggregates. Mechanistically, the LD-resident protein PLIN3 binds to the mitochondrial fusion protein MFN2, thereby relieving MFN2-mediated inhibition of MAVS and enabling its oligomerization. Furthermore, LD-mitochondria contact sites facilitate fatty acid transfer, sustaining mitochondrial membrane potential required for MAVS signaling. Oleic acid (OA)-enriched diets enhance LD formation and boost antiviral immunity in vivo, while myeloid-specific Seipin (an LD biogenesis regulator) deficiency attenuates MAVS activation and exacerbates viral susceptibility. These findings establish LDs as metabolic platforms that bridge cellular lipid metabolism with innate antiviral defense through organelle crosstalk, suggesting LD induction as a novel therapeutic strategy against viruses.
Metal-exchanged zeolites have emerged as versatile platforms for antimicrobial and antiviral applications due to their tunable pore architecture, cation exchange capacity (CEC), and ability to provide controlled metal ion release. This review critically evaluates the antibacterial and antiviral performance of silver-, copper-, and zinc-loaded natural and synthetic zeolites, with emphasis on structure-activity relationships and translational applicability. Across reported studies, metal-exchanged zeolites frequently achieve > 99% bacterial reduction or > 3-5 log₁₀ viral inactivation, depending on framework type, metal species, loading level, and contact time. Antibacterial activity is primarily associated with membrane disruption, reactive oxygen species (ROS) generation, and intracellular interference, whereas antiviral performance depends on surface adsorption, envelope destabilization, and controlled ion diffusion into virions. Compared with unmodified carriers and polymer-only matrices, metal-loaded inorganic carriers reported in the literature achieve > 99% microbial inhibition, depending on metal type, loading level, and exposure time. Natural zeolites such as clinoptilolite provide cost advantages and inherent adsorption properties but exhibit variability in composition and ion-exchange behavior. Synthetic zeolites (e.g., FAU, LTA, X, Y) offer tunable pore size, improved metal retention, and optimized release kinetics, enabling application-specific design. However, performance is strongly influenced by ion leaching behavior, cytotoxicity thresholds, environmental accumulation, and regulatory constraints in biomedical, food, textile, and water-treatment applications. Antimicrobial efficacy is governed not solely by metal identity but by the interplay between zeolite framework composition, Si/Al ratio, particle size, and ion-release dynamics. Future development requires standardized leaching assessment, long-term toxicological evaluation, and techno-economic analysis to support safe and scalable implementation.
Feline immunodeficiency virus (FIV), feline leukemia virus (FeLV), domestic cat hepadnavirus (DCHBV), felis catus gammaherpesvirus 1 (FcaGHV1), and severe fever with thrombocytopenia syndrome virus (SFTSV) are significant blood-associated pathogens impacting feline health. Because these viruses often co-circulate, rapid and simultaneous detection is essential for effective diagnosis and surveillance. A multiplex reverse transcription polymerase chain reaction (RT-PCR) assay was developed for simultaneous detection of viral and proviral nucleic acids associated with feline blood-borne viruses. Initial analytical evaluation using spike and non-spike controls established limits of detection ranging from 1.6 copies/µl (FeLV) to 900 copies/µl (FcaGHV1 and SFTSV). No cross-reactivity with other common feline viruses was observed during analytical specificity testing. When evaluated relative to corresponding singleplex RT-PCR assays (n = 126), the assay demonstrated 100% negative percent agreement and 91.9% positive percent agreement relative to corresponding singleplex RT-PCR assays, with diagnostic agreement (κ = 0.878). Following validation, the multiplex assay was applied to 442 clinical samples (401 blood and 41 spleen samples), identifying single detections in 17.2%, and codetections in 4.3% of cases. FeLV and FIV were most prevalent, while no SFTSV was detected; furthermore, FcaGHV1-positive samples underwent additional genetic characterization. Retroviral presence significantly correlated with clinically ill, male cats older than three years. Overall, the assay demonstrated reliable multiplex detection and may serve as a useful screening tool for feline viral surveillance and clinical evaluation, although negative results should be interpreted cautiously for low-copy targets.
Rapid technological advancement has led to a growing need for new materials with enhanced properties to meet the demands of emerging applications. Traditional single-component materials often fail to meet the required demands, pushing the exploration of new composite materials. In these contexts, polyhedral oligomeric silsesquioxanes (POSS) as hybrid nanomaterials exhibit excellent mechanical, thermal and chemical stability, making them ideal for advanced material design. In addition, their hydrophobic nature and ability to be functionalized enable antimicrobial properties with enhanced resistance to microbial adhesion. Compared to hybrid nanomaterials, single-component antiviral materials have limitations, including short-term durability and low surface stability. The rationale for developing the POSS-stearic acid hybrid composite is based on the ability to form a rigid nanocage framework of POSS, which provides structural robustness and enhanced stability. We show that by combining POSS with stearic acid, the hybrid material displays greater hydrophobicity than its individual components, making it an effective surface coating material that prevents the attachment of microbial pathogens, including viruses, such as human coronavirus-OC43 (HCoV-OC43) and Type A influenza virus (H1N1). We provide evidence that the present material not only serves as a barrier to viral attachment to the surface but also significantly reduces viral infectivity, possibly through direct neutralization, thereby offering a promising strategy for mitigating surface-mediated transmission of respiratory viruses.
HIV transcription is amplified by the viral transactivator Tat, yet two quantitative issues remain unresolved in chromatin: the extent to which host machinery sustains transcription in the absence of Tat, and why Tat's widespread chromatin association yields limited host-gene output. We engineered an isogenic Tat-deficient derivative of the HIVGKO dual-reporter virus that preserves native proviral architecture, enabling longitudinal measurements across diverse integration sites in primary CD4⁺ T cells and Jurkat cells. Across thousands of proviruses, host factors alone supported a restricted baseline, with Tat-null proviruses producing ∼4%-15% of wild-type protein output and remaining constrained under strong stimulation. Chromatin immunoprecipitation-seq profiling revealed that Tat is dispensable for promoter-proximal RNAPII engagement and pausing but required for efficient CDK9 recruitment, Ser2 phosphorylation, and productive elongation, defining a ceiling for Tat-independent transcription. Tat deficiency reduced overall RNAPII occupancy without increased promoter-proximal accumulation. Genome-wide mapping using Tat-null controls revealed broad Tat association with active host loci and modest increases in elongation-factor occupancy; however, host-gene RNA gains were small (∼1.05-1.49×) and poorly correlated with Tat binding. Instead, elongation-associated chromatin features better predicted responsiveness. Together, these findings define a framework separating host-driven transcription from Tat-dependent scaling and explain Tat's disproportionate potency at the provirus.
Human noroviruses are a leading cause of foodborne gastroenteritis worldwide, and oysters are a major vector for their transmission. Previous work has shown that the Psl exopolysaccharide (EPS) from oyster-derived Pseudomonas composti strain ODT-54 binds to human norovirus GII.6, but the molecular mechanism remains unknown. Here, we combined molecular docking, dynamics simulations, Molecular Mechanics Poisson-Boltzmann Surface Area calculations, and site-directed mutagenesis to investigate this interaction. Our results suggest that the composition and conformation of the B loop contribute importantly to EPS-mediated bioaccumulation, and that residue valine 297 (V297) in the B loop of the GII.6 (KX752057.1) P domain is an important determinant of Psl binding. Our findings provide residue-level evidence that the composition and conformation of the B loop, particularly residue V297, contributes to the interaction between human norovirus GII.6 and the bacterial Psl exopolysaccharide. The persistence of human noroviruses in environmental and food matrices can be facilitated by their interaction with bacterial surface components, such as exopolysaccharides (EPS). However, the molecular basis of norovirus-bacteria interactions remains poorly understood. In this study, we demonstrate that the GII.6 norovirus capsid protein specifically binds to the Pseudomonas-derived Psl EPS via a key residue, valine 297, located in the hypervariable B loop of the P2 subdomain. This interaction is genotype-specific, with GII.6 exhibiting significantly stronger binding than the epidemic GII.4 strain. Our findings reveal a previously unrecognized mechanism of viral environmental persistence mediated by bacterial EPS and highlight the role of capsid loop flexibility and residue-level variation in shaping norovirus-host-environment interactions. This work provides a structural and dynamic framework for understanding norovirus ecology and may inform future strategies for mitigating viral contamination in food and water systems.
Chronic Kidney Disease (CKD) is a significant global health challenge, particularly among people living with HIV (PLHIV) on antiretroviral therapy (ART). The combined effects of HIV infection, long-term ART exposure, and other comorbidities increase CKD risk in this population. Despite international and national recommendations for routine CKD screening, the uptake remains inconsistent in resource-limited settings like Tanzania. Understanding the prevalence and associated factors of CKD screening is vital for improving early detection and patient outcomes. This study aimed to determine the prevalence of CKD screening and associated factors among PLHIV on ART in Dar es Salaam, Tanzania. This was a hospital-based cross-sectional study conducted in Dar es Salaam, Tanzania. Data were collected using a semi-structured questionnaire and the review of medical records. A systematic random sampling method was used to recruit participants in the study. Descriptive analysis was used to summarize participants' characteristics and the prevalence of CKD screening. Univariate and multivariate logistic regression were applied to identify factors associated with CKD screening, with a p-value < 0.05 considered for statistical significance. Among 426 adults on ART, CKD screening uptake was high (94.1%). Screening was more likely among participants with higher CD4 counts (>350 cells/µL; AOR: 9.73, 95% CI: 1.21, 78.16; p = 0.032), and less frequent ART clinic attendance was associated with lower screening odds (every six months vs. monthly; AOR: 0.16, 95% CI: 0.05, 0.48; p = 0.001). Interestingly, participants reporting provider recommendations for CKD screening had lower odds of screening (AOR: 0.17, 95% CI: 0.04, 0.79; p = 0.024). Sociodemographic factors, viral load status, comorbidity, perceived adequacy of CKD information, and distance to screening facilities were not significantly associated with CKD screening. CKD screening uptake among adults on ART was high, but screening was influenced by clinical and service factors. Higher CD4 counts and more frequent clinic attendance were associated with increased screening, while provider recommendations were paradoxically linked to lower screening, highlighting gaps in translating advice into action. Strengthening integrated, patient-centered approaches and ensuring systematic CKD screening across all patient groups is essential to optimize early detection and management of kidney disease in PLHIV.
Chronic hepatitis B (CHB) affects approximately 250 million people worldwide. The major barrier to cure lies in the persistent presence of covalently closed circular DNA (cccDNA) and integrated HBV DNA within hepatocytes, which continuously drive hepatitis B surface antigen (HBsAg) expression and maintain immune tolerance, thereby leading to functional exhaustion of antiviral effector cells. Although nucleos(t)ide analogues (NAs) effectively suppress viral replication, they have limited impact on cccDNA activity and antigen production. In contrast, pegylated interferon-α (PEG-IFN-α) enhances antigen presentation, activates innate immunity, and partially restores HBV-specific T cell function, thereby contributing to the disruption of immune tolerance to some extent. However, its therapeutic efficacy remains influenced by host immune status and antigen burden. With the development of antigen-reduction strategies (such as siRNA/antisense oligonucleotides [ASO] and HBsAg-targeting monoclonal antibodies), therapeutic vaccines, and immune-modulatory approaches, PEG-IFN-α is increasingly being incorporated into combination therapies. This review summarizes its immunological basis and clinical advances, and further discusses biomarker-driven patient stratification strategies, with the aim of improving functional cure rates in CHB.
Insect-borne viruses represent a major threat to global agriculture and public health. Rice ragged stunt virus (RRSV), a destructive pathogen transmitted by brown planthopper (Nilaparvata lugens Stå), lacks comprehensive understanding of the molecular mechanisms underlying its replication and transmission. This study reveals that the RRSV P6 protein serves as a key regulator of vector-borne transmission by sequentially interacting with RTE1-HOMOLOG 2 (OsRTH2) and ETHYLENE-INSENSITIVE3-LIKE 2 (OsEIL2) in the host ethylene signaling pathway. This biphasic strategy manipulates brown planthopper (BPH) behavior, initially promoting viral replication and subsequently facilitating epidemic spread. Furthermore, the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) significantly impairs BPH fitness, reducing survival and fecundity. Our study elucidates how a plant virus manipulates the host ethylene signaling pathway to promote its own replication and transmission. Moreover, we identify the ethylene biosynthesis precursor ACC as a potential, environmentally friendly control agent against brown planthoppers. © 2026 Society of Chemical Industry.
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Infectious viral diseases remain a major and persistent threat to human health, and findings from animal models often translate poorly to clinical applications. Here, we constructed protein interactomes for seven species, including humans, revealing substantial differences in research biases. A random sampling strategy was employed to generate human interactomes, with sizes matched to those of the other six species to ensure cross-species comparability. We found that the clustering of virally targeted proteins within the interactomes (measured as largest connected component [LCC] proportion) and network fragmentation after their removal correlated with network density. Viral perturbations in species other than humans were heterogeneous, but generally showed reduced clustering and increased network fragments. The relative degree of network fragmentation (quantified by relative IC values) was correlated with local network conservation rather than sequence similarity, indicating that local network structure is selected, maintaining resilience during virus-host interactions. Furthermore, relative IC values and LCC proportion differences were positively associated with non-vaccine therapeutic success rates from phase I trials to approval. Our findings present a novel paradigm for the comparative analysis of disease phenotypes across species, thereby providing a new evaluative metric for selecting animal models in translational biomedical research.IMPORTANCECross-species network comparisons help uncover the molecular mechanisms of complex phenotypes. The viral module formation within interactomes and the network resilience during viral infection are of key impacts on hosts. The analysis of the interactomes of seven species shows that network density critically influences the network metrics performance. Under size-matched conditions, non-human species exhibited more complex viral perturbations than humans, but with smaller viral module size and more network fragmentation. The difference in fragmentation had a positive correlation with the conservation of the local network structure of virally targeted proteins, implying that viral perturbations act as evolutionary signals at the network level. Additionally, differences in fragmentation and viral module size were positively associated with the rates of successful progression from phase I trials to approval. This work offers a new framework for cross-species disease analysis and guides model organism selection for viral infection research.
Positive-sense RNA viruses that constitute a large class of human pathogens employ various strategies to suppress and evade host immune defenses. Understanding the dynamic interaction between the viral life cycle and immune signaling is crucial to designing effective antiviral strategies. Although significant progress has been made, quantitative models that can accurately capture the intricate interactions and the intertwined dynamics during viral infection of cells remain missing. In this study, we develop a comprehensive mathematical model that integrates the intracellular viral life cycle with key cellular innate immune pathways, including RIG-I-mediated detection and JAK-STAT signaling. The model provides mechanistic insights into long-standing observations, capturing both virus-specific dynamics and innate immune response, and the key components driving their coupled dynamics. For example, a comparison of viruses shows how the Japanese Encephalitis virus undergoes a dramatic reduction in viral load in cells, due to its rapid replication that robustly activates the RIG-I pathway, in contrast to the poor immune control of Hepatitis C virus. More importantly, our model demonstrates how virus-host interactions exhibit a sharp transition boundary behavior, where minor differences in immune strength or viral suppression capacity can determine whether infections resolve or persist. We propose that ISG mRNA translation and viral replication predominantly dictate these bimodal infection outcomes. Additionally, the model not only recapitulates IFN desensitization but also identifies the molecular players involved. We demonstrate how our model's ability to capture IFN dynamics allows us to predict optimal timing and dosing strategies for interferon-based prophylactic therapies. Together, our approach reveals fundamental features that govern the delicate balance between the establishment of infection and immune control in RNA virus infections.
The coronavirus disease 2019 pandemic illustrated the need to develop medical countermeasures against emerging infectious diseases. As viruses rely on cellular machinery for replication, host-directed antivirals (HDAs) may complement conventional antiviral strategies in a manner that offers broad-spectrum efficacy, including against novel viruses, and a potentially higher barrier to viral escape. Despite their potential, HDAs are under-represented as therapeutics, partly due to a lack of consensus on druggable host targets. To address this, we have performed a meta-analysis of 62 functional genomics studies involving viral families of pandemic concern, including Arenaviridae, Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae, Paramyxoviridae, Phenuiviridae, Picornaviridae, Poxviridae and Togaviridae. Using a RRA and protein-protein interaction network approach, host factors and cellular processes required by multiple virus families were identified, including the V-type ATPase complex, glycosaminoglycan synthesis, Golgi trafficking and endoplasmic reticulum membrane protein insertion. These pathways include those with known relevance to infection by some viruses while providing novel insights into the life cycles of others. Therapeutic targeting of these top ranked host factors is also discussed, with several already possessing small-molecule inhibitors, highlighting their therapeutic potential. Antivirals are an essential component of medical countermeasures against viral disease and fulfil a complementary role to vaccines. Importantly, they may provide the only therapeutic option for pathogens lacking effective vaccines or for individuals unable to be vaccinated. This analysis furthers our understanding of the virus-host interface and nominates cellular targets for the future development of HDAs as medical countermeasures for pandemic resilience.
White spot syndrome virus (WSSV) devastates shrimp aquaculture, yet safe antivirals remain scarce. Here we identify a druggable host-directed pathway centered on hemocyanin (HMC). This pathway coordinates endoplasmic reticulum (ER)-mitochondrial crosstalk to promote WSSV replication, which could be counteracted by the natural anthraquinone emodin. In Litopenaeus vannamei, emodin suppressed viral replication with a half maximal inhibitory concentration (IC50) of 1.174 μM, improved survival in both therapeutic and prophylactic regimens, remained effective after per os administration, and retained antiviral activity in water for up to 4 d. Target fishing, orthogonal biophysics, and docking analyses show that emodin binds HMC (Kd = 4.49 μM) and interferes with HMC-HSPA5/BiP (heat shock protein family A (Hsp70) member 5) association. Mechanistically, emodin weakens the ITPR/IP3R (inositol 1,4,5-trisphosphate receptor)-VDAC (voltage dependent anion channel)-MCU (mitochondrial calcium uniporter) conduit at ER-mitochondrial contact sites, thereby limiting Ca2+ transfer, restoring mitochondrial membrane potential and organelle spacing, and attenuating ER stress. Untargeted metabolomics revealed that WSSV induced phosphoinositide and amino acid dysregulation, whereas emodin selectively normalizes phosphatidylinositol (PtdIns) and phosphatidylinositol 1,4,5-trisphosphate (PtdIns[1,4,5]P3) signaling and rebalances amino acid, tricarboxylic acid (TCA) intermediates. Correspondingly, emodin inhibited phosphoinositide 3-kinase (PI3K)-AKT/protein kinase B-MTOR (mechanistic target of rapamycin kinase) complex 1 (MTORC1) signaling and restored lysosome-dependent macroautophagy/autophagy. HMC RNAi or ITPR and MCU inhibition phenocopied emodin, whereas exogenous HMC or ER stress activation exacerbated infection and was mitigated by emodin or MCU blockade. These findings establish HMC-anchored ER-mitochondrial contact as a central proviral vulnerability and position emodin as a practical scaffold for next-generation antivirals in aquaculture.
Northeastern China is a recognized hotspot for tick-borne viral diseases. However, there remains a lack of methods capable of simultaneously detecting these emerging and re-emerging tick-borne viruses. Primer and probe sets were designed using Beacon Designer 8.0, targeting conserved regions of viral genomes from Alongshan virus (ALSV), Tick-borne encephalitis virus (TBEV), Severe fever with thrombocytopenia syndrome virus (SFTSV), Beiji nairovirus (BJNV), Yezo virus (YEZV), and Songling virus (SGLV). Recombinant plasmids were constructed to assess assay sensitivity, while virus-positive cDNA from tick samples was used to verify specificity. The performance of these assays was further validated using field-collected tick samples, with results compared against established reference methods serving as gold standards. Specific primer and probe sets were designed with amplicon lengths ranging from 83 to 199 bp. Optimization of the reaction components yielded final primer volumes of 0.2-0.5 μL and probe volumes of 0.4-1.0 μL (from 10 μM working stocks). Sensitivity analysis demonstrated a limit of detection (LOD) as low as 10 copies/μL for all six viruses, while specificity testing confirmed no cross-reactivity among the targets. In validation trials, the established TaqMan RT-qPCR assays showed complete concordance with reference methods for ALSV (5/15) and TBEV (4/14). Notably, the TaqMan assays identified additional positive samples for SFTSV (n=1), BJNV (n=3), and YEZV (n=1) that were missed by the reference assays, particularly in samples with low viral loads. Conversely, two samples that tested positive for SGLV using SYBR Green RT-qPCR yielded negative results with the TaqMan RT-qPCR assay. We have successfully developed a suite of highly sensitive and specific single-plex TaqMan RT-qPCR assays for the rapid detection of six key tick-borne viruses in northeastern China. These assays facilitate efficient viral surveillance in tick populations and provide a diagnostic tool with significant potential for clinical applications.
Deep mutational scans across receptor-binding domains (RBDs) of diverging SARS-CoV-2 variants reveal ongoing changes to the effects of mutations, a phenomenon known as epistasis. Careful accounting for these altered mutational effects is important in viral surveillance and forecasting, and more broadly, for understanding the impacts of epistasis on real-world viral evolutionary trajectories. Using a yeast-display RBD deep mutational scanning (DMS) platform, we measure the impacts of virtually all single amino acid mutations and single-residue deletions in the Omicron KP.3.1.1 and LP.8.1 RBDs on folded RBD expression and binding affinity for the human ACE2 receptor. Our comprehensive maps reveal patterns of evolutionary accessibility and constraint at single-residue resolution and, when compared to prior datasets, highlight sites whose amino acid preferences continue to change across viral variants. Notably, sites 455, 456, and 493 - which have exhibited repeated substitutions and epistatic dependencies across Omicron subvariants going back to BA.1 - again demonstrate altered patterns of mutational accessibility and constraint. Therefore, it appears that these hotspots of repeated RBD evolution have not yet converged on fixed amino acid solutions but instead remain sites of ongoing epistatic reconfiguration. We compare our measurements of direct RBD:ACE2 affinity with recently published measurements of mutation impacts on ACE2 binding in the full quaternary spike context, which also integrates the effects of spike conformational dynamics; our analysis uncovers mutations like H505W that could favor adoption of the down/closed RBD conformation as a viral strategy for future antigenic evolution.
This review aims to address the therapeutic potential of new generation of oncolytic viruses (OVs) for liver cancer with the focus on hepatocellular carcinoma (HCC). We evaluate the therapeutic status of oncolytic virus therapy (OVT) for liver cancer, addresses the research question of how different OVs perform in treating the malignancy, and and analyze the challenges remain in their clinical treatment based on the synthesis of both preclinical and clinical studies investigating various OVs, including Herpes simplex virus (HSV), Adenovirus (AdV), Vaccinia virus (VV), Coxsackievirus (COX), and Newcastle disease virus (NDV). OVs selectively infect and lyse tumor cells, stimulating anti-tumor immunity. HSV and VV have demonstrated high efficacy and safety in studies. Genetically engineered AdV and NDV platforms, especially those expressing immune checkpoint inhibitors or cytokines, show promising anti-tumor activity. Advances in viral engineering and delivery systems have improved tumor selectivity and immune activation. Key challenges identified include host antiviral immunity, delivery efficiency, and optimal patient selection. OVT represents a promising immunotherapeutic strategy for liver cancer. While significant progress has been made in both efficacy and safety through genetic modification, ongoing innovation in viral engineering, combination therapies.
This report presents a 6-year antigen-based surveillance of pediatric viral gastroenteritis in Turkey, revealing substantial epidemiological shifts during and after the coronavirus disease 2019 (COVID-19) pandemic. Adenovirus circulation was strongly affected by COVID-19-related public health restrictions, showing a marked decline during restriction periods. However, rotavirus exhibited a relative increase in 2021 despite ongoing restrictions, followed by a more pronounced rise after the relaxation of measures, aligning with the "immunity debt" hypothesis associated with altered early-life viral exposure. These findings illustrate how pandemic-related interventions reshaped the circulation of enteric viruses and underscore the value of routine rapid antigen testing for detecting post-pandemic resurgences, which is underexplored in the literature. In der vorliegenden Arbeit wird eine 6 Jahre dauernde antigenbasierte Beobachtungsstudie zur pädiatrischen viralen Gastroenteritis in der Türkei vorgestellt, mit dem Ergebnis wesentlicher epidemiologischer Verschiebungen während und nach der COVID-19-Pandemie. Die Verbreitung von Adenoviren war durch Gesundheitsvorschriften aufgrund von COVID-19 stark eingeschränkt – mit einer deutlichen Abnahme während der Phasen mit geltenden Restriktionen. Rotaviren wiesen jedoch im Jahr 2021 trotz weiterhin geltender Restriktionen einen relativen Anstieg auf, mit einem anschließenden deutlicheren Anstieg nach Lockerung der Maßnahmen – in Einklang mit der Hypothese der „Immunitätsschuld“ in Zusammenhang mit veränderter Virusexposition in einem frühen Lebensabschnitt. Diese Ergebnisse zeigen, wie pandemiebezogene Maßnahmen die Verbreitung von Darmviren neu gestalten und unterstreichen den Wert der routinemäßigen schnellen Antigentestung zur Erkennung des postpandemischen Wiederauftretens, das in der Literatur noch zu wenig erforscht ist.