Search Results (1,075)

RNA viruses pose a persistent global threat due to their high mutation rates, zoonotic potential, and rapid adaptability. Emergence events have risen steadily, as demonstrated by major outbreaks caused by Influenza A, Ebola, Zika, and Chikungunya viruses, followed by the coronavirus epidemics of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-1) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and culminating in the COVID-19 pandemic. These characteristics frequently compromise the durability of existing vaccines and antiviral therapies, highlighting the urgent need for new antiviral agents. Alkaloids, a structurally diverse class of nitrogen-containing natural compounds, have gained attention for their ability to interfere with multiple stages of the viral life cycle, including entry, replication, protein synthesis, and host immune modulation. To our knowledge, this review compiles all currently reported alkaloids with antiviral activity against RNA viruses and summarizes their proposed mechanisms of action, distinguishing evidence from in vitro, in vivo, and in silico studies. Quaternary alkaloids are discussed separately because their permanent ionic charge enables distinctive interactions with membranes and host pathways. Although many findings are promising, clinical translation remains limited by incomplete mechanistic validation, scarce in vivo data, suboptimal bioavailability, narrow therapeutic windows, and inconsistent experimental methodologies. To advance the field, future research should prioritize RT-qPCR–based antiviral evaluation to accurately quantify viral replication, incorporate mechanistic assays to clarify modes of action, apply structure–activity relationship (SAR) approaches for rational optimization, and expand in vivo pharmacokinetic and efficacy studies to assess therapeutic feasibility. Overall, alkaloids represent a promising yet underdeveloped reservoir for next-generation antiviral discovery against rapidly evolving RNA viruses. Full article

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, primarily driven by chronic inflammation from viral hepatitis, metabolic dysfunction, alcohol-induced liver disease, and cirrhosis. Conventional therapies often fail in advanced stages, highlighting the need for mechanism-based, precision-guided interventions. Plant-derived secondary metabolites represent a promising class of bioactive compounds with structural diversity, multitarget activity, anti-inflammatory effects, and favorable toxicity profiles. This review follows a semi-systematic narrative that synthesizes preclinical and experimental evidence on the anti-inflammatory and anticancer properties of key phytochemicals, including epigallocatechin-3-gallate, galangin, resveratrol, quercetin, curcumin, berberine, genistein, and thymoquinone. These compounds consistently modulate critical inflammation-driven signaling pathways, PI3K/AKT/mTOR, NF-κB, JAK/STAT, Wnt/β-catenin, and MAPK, resulting in apoptosis induction, cell cycle arrest, inhibition of angiogenesis, and reduced invasion and metastasis in multiple HCC models. Despite strong preclinical evidence, clinical translation remains limited by variable bioavailability, incomplete safety data, and insufficient human studies. A staged development strategy is recommended: standardized formulations, Good Laboratory Practice-compliant pharmacokinetic/toxicology studies, validation in patient-derived models, and early-phase, biomarker-guided clinical trials with combination therapy arms. Addressing regulatory, manufacturing, and quality control considerations will be essential for advancing these compounds as adjuvant or complementary agents in precision HCC therapy. Full article

The global swine industry suffers persistent economic losses and health challenges due to major viral pathogens such as African swine fever virus (ASFV), porcine reproductive and respiratory syndrome virus (PRRSV), classical swine fever virus (CSFV), and porcine circovirus (PCV). Traditional diagnostic methods, including virus isolation, serology, and quantitative PCR (qPCR), are limited by time, equipment requirements, and field applicability. Recent advances in CRISPR-based diagnostics, particularly those leveraging the collateral cleavage activity of Cas12a and Cas13a, have enabled rapid, sensitive, and field-deployable nucleic acid detection. This review outlines the principles of CRISPR-Cas12a/13a systems, their integration with isothermal amplification techniques, and their application in detecting major swine viruses. Cas12a-based platforms (e.g., DETECTR) and Cas13a-based systems (e.g., SHERLOCK) achieve detection limits as low as single-copy/μL within 25–60 min at 37 °C, offering high specificity and compatibility with visual readouts. Applications include ASFV, PRRSV, CSFV, PCV, foot-and-mouth disease virus (FMDV), porcine rotavirus (PoRV), and porcine parvovirus 7 (PPV7). Despite significant advances, challenges remain, notably the reliance on nucleic acid extraction and the need for fully integrated “sample-in, result-out” systems. Ongoing innovations in extraction-free methods, lyophilized reagents, and multiplex detection will strengthen the role of CRISPR diagnostics in swine disease surveillance and control. From an application standpoint, the technology offers a low-capital, field-adaptable alternative to qPCR, with its value proposition rooted in early outbreak containment and loss prevention. Its adoption pathway is expected to vary across production systems—serving as a sentinel tool in intensive settings, a leapfrogging solution in rapidly intensifying regions, and through shared-service models in resource-limited contexts. However, translation to routine use still requires overcoming standardization hurdles, regulatory validation, and workflow integration. Full article

The development of next-generation HIV-1 therapeutics, including ultralong-acting antivirals, novel mechanistic classes, and curative immunotherapies, promises to overcome the limitations of lifelong, daily antiretroviral therapy (ART). However, the real-world efficacy of these treatments depends on the complex epidemiological landscapes in which they are used. In South America, HIV-1 epidemics intersect hyperendemic arboviruses, including dengue, Zika, chikungunya, and yellow fever, and regionally isolated pathogens, such as mammarenaviruses. These co-infections cause profound episodic immune activation and organ dysfunction that alter drug pharmacokinetics, disrupting healthcare access and adherence. These factors can compromise ART efficacy, promote resistance, and influence latent reservoir dynamics. This review synthesizes clinical and translational evidence of this intersection. We evaluate how emergent agents, such as capsid inhibitors (lenacapavir), long-acting injectables (cabotegravir/rilpivirine), maturation inhibitors (GSK3640254), and broadly neutralizing antibodies (bNAbs), perform in the context of co-endemic viral challenges. Specifically, we argue that therapeutic development must become “co-infection-aware” to progress toward a cure and achieve durable HIV-1 control. We provide a translational roadmap that explicitly incorporates co-infection endpoints into clinical trials, develops preclinical models that better reflect real-world viral exposures, and prioritizes implementation strategies that remain effective in the case of recurrent outbreaks. Integrating regional viral ecology into HIV-1 therapeutic research is therefore a necessary step toward developing interventions that are durable and effective on a global scale. Full article

Background/objectives. Emerging viral diseases represent an increasing threat to global health security, driven by environmental change, globalization, and intensified human–animal–environment interactions. The COVID-19 pandemic exposed critical weaknesses in preparedness systems but also demonstrated the transformative potential of recombinant vaccine technologies, which enable rapid, scalable, and safe responses to novel pathogens. We aim to examine the role of recombinant vaccine platforms in the management of emerging viral diseases, emphasizing their contribution to health system preparedness and exploring strategies for their integration into preparedness frameworks. Methods. We synthesized the current evidence on recombinant vaccine platforms (viral vector, protein subunit, DNA, and mRNA) through a targeted review of the scientific literature, regulatory documents, and global health policy reports. Drawing from experiences like COVID-19 (mRNA vaccines) and Ebola (rVSV-ZEBOV), we analyzed the advantages, challenges, and lessons from initiatives such as the CEPI, BARDA, HERA, and WHO frameworks. Results. Recombinant vaccine platforms offer significant advantages for epidemic preparedness through rapid adaptability, standardized production, and strong safety profiles. Nonetheless, challenges remain in manufacturing scalability, cold-chain logistics, regulatory harmonization, and equitable global access. Global initiatives such as the CEPI, WHO-led programs, BARDA, and regional manufacturing networks exemplify this collaborative approach, while regulatory mechanisms have proven to be essential to timely vaccine deployment. Conclusions. Recombinant vaccines have redefined preparedness by coupling scientific innovation with operational agility. Strengthening global coordination, regional production capacity, and public trust is essential to ensure that technological progress translates into equitable and effective public health impacts. Full article

Mouse Mammary Tumor Virus (MMTV) is an established mammary carcinogen in mice, yet the relevance of MMTV-like agents to human breast cancer remains debated. Across cohorts worldwide, PCR-based detection of MMTV-like DNA, in situ RNA localization, and immunohistochemical detection of viral proteins have been reported in a subset of tumors and, in some studies, in pre-invasive lesions; however, results are heterogeneous and vulnerable to methodological confounding, including murine DNA contamination and variable assay design. Here, we synthesize the evidence through a causality-oriented framework that integrates (i) standardized multi-target detection with mandatory contamination controls, (ii) epidemiologic designs that explicitly stratify sporadic versus hereditary/BRCA-driven disease, and (iii) mechanistic endpoints that are demonstrably human-relevant (e.g., in situ viral RNA/protein in tumor cells, integration-site mapping, and functional consequences of viral gene products in human models). Given current evidence, the overall causal plausibility is best considered “possible,” rising to “probable” only for a restricted subset of sporadic tumors, provided that future studies verify bona fide infection in situ using standardized multi-target assays, rigorous murine exclusion controls, and mechanistic evidence linking viral expression and/or integration to tumor cell biology. Without these endpoints, association studies alone are unlikely to resolve causality or enable meaningful clinical translation. Full article

Plant RNA interference (RNAi) is a fundamental antiviral defense that relies on coordinated activities of DICER-like endonucleases (DCLs), Argonaute proteins (AGOs) and RNA-dependent RNA polymerases (RDRs). Over the past decades, studies using model and crop species have uncovered complex and often redundant roles for DCLs and RDRs in generating and amplifying virus-derived small interfering RNAs (vsiRNAs), in addition to connections with transcriptional gene silencing (TGS) and epigenetic defenses against DNA viruses. Concurrently, plant viruses have evolved diverse counterstrategies—proteinaceous RNA silencing suppressors (RSSs), exoribonuclease (XRN)-resistant noncoding RNAs, and indirect manipulation of host pathways—to evade RNAi. Driven by the co-evolutionary arms race, plants have developed sophisticated counter-countermeasures that modulate or overcome viral anti-RNAi activity. Accumulated evidence suggests that plants encode host factor genes that are activated to degrade or sequester viral components such as RSSs against viral infection. On the other hand, plants have also evolved endogenous host modulators of antiviral RNAi that can either reinforce the antiviral response or be co-opted by viruses to antagonize it, representing a furious dynamic molecular battling mechanism. Here, we review recent advances in the molecular functions of DCLs and RDRs across species, summarize newly discovered viral counter-defenses (including RNA-based suppressors), and discuss host counter-countermeasures. We research key areas—such as the roles of RDRγ-class proteins, RTL1 (RNase three-like 1)-mediated competition with DCLs, and the mechanistic impact of viral noncoding RNAs—and outline translational opportunities for improving virus resistance in crops through breeding, biotechnological approaches, and RNA-based applications. Full article

Objectives: To synthesize current evidence and emerging data on systemic treatment strategies for early-stage and locally advanced human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), with emphasis on treatment de-escalation and the integration of immunotherapy. Data Sources: We searched PubMed/MEDLINE, Scopus, and EMBASE for English-language studies published from 2010 to 2025 using terms related to HPV-positive disease, oropharyngeal carcinoma, de-escalation, chemoradiation, and immunotherapy. Review Methods: Peer-reviewed clinical trials, meta-analyses, and key translational studies addressing systemic therapy, biomarkers, and immunotherapeutic strategies in HPV-positive OPSCC were included. Emphasis was placed on phase II–III trials evaluating cisplatin-sparing regimens, cetuximab substitution, radiation dose reduction, and early-phase immunotherapy combinations. Evidence was synthesized qualitatively. Results: Cisplatin-based concurrent chemoradiation remains the standard of care for locally advanced HPV-positive OPSCC. De-intensification trials suggest that reduced-intensity regimens may be feasible in carefully selected low-risk patients; however, replacing cisplatin with cetuximab results in inferior survival. PD-1 inhibitors (e.g., pembrolizumab, nivolumab) provide durable responses in recurrent/metastatic disease and are under active evaluation in earlier stages and in combination with therapeutic vaccines, bispecific antibodies, and viral-vector platforms. Conclusions: Systemic therapy for HPV-positive OPSCC is moving toward biomarker-informed personalization. Cisplatin-based chemoradiation remains the curative backbone, while rational de-escalation and immunotherapy integration may preserve high cure rates while reducing long-term toxicity. Ongoing phase III trials will clarify which patient subsets are most suitable for de-intensified or immunotherapeutic approaches, guiding future standards of care. Full article

Synthesized by expressing natural collagen sequences in specific hosts, recombinant collagen exhibits multiple advantages, encompassing a higher content of bioactive domains, enhanced antioxidant activity, the absence of viral pathogens, favorable hydrophilicity, reproducible production, and low immunogenicity. Consequently, it has found extensive use in applications ranging from biomaterials and pharmaceuticals to skincare. This review systematically explores various expression systems for recombinant collagen, including those utilizing Escherichia coli, Pichia pastoris, plants, insect baculovirus, and mammalian cells. It provides a detailed comparison of their differences and commonalities in terms of production efficiency, post-translational modification capability, and cost-effectiveness. Key separation and purification techniques for recombinant collage-notably precipitation, affinity chromatography, ion-exchange chromatography, and gel filtration chromatography are further introduced, with an in-depth analysis of the applicable scenarios and purification outcomes for each method. Finally, the review comprehensively summarizes the characterization methods for both the physicochemical properties and biological functions of recombinant collagen. For physicochemical properties, techniques covered include scanning electron microscopy, micro-differential thermal analysis, circular dichroism spectroscopy, SDS-PAGE, mass spectrometry, and Fourier-transform infrared spectroscopy. For biological functions, the focus is on its roles and the corresponding assessment methods in processes such as cell proliferation, migration, adhesion, and wound healing. Building upon this comprehensive overview, current challenges facing recombinant collagen are identified, and future directions are proposed, emphasizing the need to reduce R&D costs, refine testing methods for cosmetic products, and improve safety evaluation protocols to advance the field. Full article

Comparative transcriptomics offers a powerful approach to elucidate host–virus interactions across related pathogens, yet systematic evaluations across species-matched cellular systems remain limited. We performed a cross-species RNA sequencing analysis of respective species’ cells infected with three alphaherpesviruses—herpes simplex virus 1 (HSV-1), bovine alphaherpesvirus 1 (BHV-1), and equid alphaherpesvirus 1 (EHV-1)—to dissect conserved and virus-specific transcriptional responses. We show that certain orthologous genes and orthologous pathways are differentially regulated upon infection among the three species like pathways related to translation rRNA processing and TNF-alpha signalling. We find that the earliest sampled timepoint of infection, 2 h post infection (hpi), shows the most commonly enriched pathways among the three species compared to later timepoints. At 6 h and 9 h post infection, BHV-1- and EHV-1 infections have more in common with each other in terms of enriched pathways than with HSV-1 infections. Moreover, we provide a comprehensive analysis of temporal viral gene expression for all three herpesviruses. Together, these findings provide a comparative framework for understanding alphaherpevirus–host interactions and reveal both conserved core responses and species-specific transcriptional signatures. This work establishes a foundation for identifying broadly acting antiviral targets as well as virus-specific vulnerabilities that may inform host-directed therapies and cross-species disease management. Full article

Curcumin, the major polyphenolic constituent of Curcuma longa, has been widely investigated as a hepatoprotective adjunct due to its antioxidant and immunomodulatory properties. This review evaluates the relevance of curcumin for the prevention and management of liver dysfunction and hepatitis in pigs by synthesizing available porcine evidence and integrating mechanistic insights from translational liver injury models where pig-specific data remain limited. Across experimental hepatic injury contexts, curcumin administration is most consistently associated with reduced biochemical and structural indicators of hepatocellular damage, including decreased aminotransferase activity, attenuation of lipid peroxidation, and enhancement of endogenous antioxidant defenses. These effects are mechanistically linked to suppression of pro-inflammatory signaling pathways, particularly NF-κB-related transcriptional activity and inflammasome-associated responses, together with reduced expression of key cytokines such as TNF-α, IL-1β, and IL-6. Concurrent activation of Nrf2-centered cytoprotective pathways and induction of phase II antioxidant enzymes (including HO-1, GST, and NQO1) appear to constitute a conserved axis supporting hepatic oxidative stress resilience. In swine-relevant infectious settings, available data further support antiviral activity against selected porcine pathogens, including classical swine fever virus and porcine reproductive and respiratory syndrome virus, potentially mediated through interference with lipid-dependent stages of viral replication and modulation of Kupffer cell activation. Although combination strategies with established hepatoprotective approaches are conceptually attractive, current synergy evidence remains heterogeneous and largely extrapolated. Overall, curcumin represents a plausible adjunct candidate for supporting porcine liver health; however, translation into practice will depend on resolving formulation-dependent bioavailability constraints and strengthening the pig-specific evidence base. Full article

Carbon dots (CDs) have emerged as a promising non-viral gene delivery vector due to their excellent biocompatibility and tunable surface properties. In this study, four CDs with gradient-positive zeta potentials (7.23 mV, 16.7 mV, 25.3 mV, 34.5 mV) were synthesized via a hydrothermal method. Among these, CDs-3 with an optimal zeta potential of 25.3 mV stood out, exhibiting ultra-low cytotoxicity (cell viability > 80% even at 50 μg/mL) and a transfection efficiency of nearly 100% (for GFP plasmid delivery), significantly outperforming commercial vectors Lipo2000 and PEI. A stable CDs-3/siIhh delivery system was constructed at a mass ratio of 2:1. In vitro evaluations confirmed that CDs-3/siIhh could efficiently regulate the Indian Hedgehog (Ihh) signaling pathway and osteoarthritis (OA)-related markers in both normal and IL-1β-induced inflammatory ATDC5 chondrocytes. Its regulatory effect was significantly superior to that of the commercial Lipo2000/siIhh and PEI/siIhh systems. This consistent “transcription–translation” regulation, combined with the carrier’s safety and excellent cellular internalization capacity in chondrocytes, highlights its potential for OA gene therapy. Collectively, our work develops a novel, safe, and efficient positive-potential CD-based gene delivery vector, providing a promising gene regulatory capacity by leveraging optimized surface charge engineering. Full article

Mucosal-associated invariant T (MAIT) cells exist in high numbers in the body and have a unique and highly conserved T cell receptor (TCR). They can be activated in a TCR-dependent manner by ligands presented on the monomorphic protein MHC class I-related protein 1 (MR1) which is found on many cell types, including professional antigen presenting cells (APCs) and epithelial cells. This has sparked interest in the potential to exploit the MR1-MAIT cell axis for the development of vaccines against infectious disease. Within this context an MR1 ligand, typically 5-(2-oxopropylideneamino)-d-ribitylaminouracil (5-OP-RU), is administered with or without a Toll-like receptor (TLR) ligand or cytokine in a pan vaccination approach that would prime the immune response to provide protection against a variety of bacterial and viral pathogens. This strategy has led to enhanced protection in murine models of Legionella longbeachae, Francisella tularensis, Klebsiella pneumoniae, Streptococcus pneumoniae and influenza infection. However, studies against Mycobacterium tuberculosis infection have proven less successful. The second vaccination approach involves pairing the MR1 ligand with more conventional antigens that could activate CD4⁺ and/or CD8⁺ T cells. This approach has been successful in murine models of cholera, influenza, and SARS-CoV-2, including in the context of subunit vaccines. However, there are several challenges when using MR1-MAIT cell-mediated vaccine adjuvants. These include the inherent instability of 5-OP-RU and the need for more advanced studies to better understand how the use of MR1 ligands would translate to applications in humans. This review will discuss these aspects and highlight the mechanistic studies that have been undertaken to understand how MAIT cells might elicit their effects within the context of MAIT cell-mediated vaccines for infectious disease. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is initiated by the viral spike proteins, which are key structural components that mediate host cell binding and entry and alter downstream signaling through multiple interactions with endothelial surface receptors. Endothelial dysfunction is a central consequence of COVID-19, contributing to vascular inflammation, barrier disruption, thrombosis, and multi-organ injury affecting the pulmonary, cardiovascular, cerebral, and renal systems. Emerging evidence demonstrates that spike protein-mediated effects, independent of productive viral infection, disrupt endothelial homeostasis through angiotensin-converting enzyme 2 (ACE2) dysregulation, integrin engagement, altered calcium signaling, junctional protein remodeling, oxidative stress, and pro-inflammatory and pro-apoptotic pathways. This review is intentionally focused on spike (S) protein-driven mechanisms of endothelial dysfunction; pathogenic vascular effects attributed to other SARS-CoV-2 structural proteins, including the nucleocapsid (N) protein, are beyond the scope of this discussion. In this review, we synthesize current experimental and translational data detailing the molecular mechanisms by which the SARS-CoV-2 spike protein drives endothelial dysfunction across multiple organ systems and discuss potential therapeutic strategies aimed at preserving endothelial integrity in acute COVID-19 and its long-term vascular sequela. Full article

Potyvirus genomes are expressed as a single large open reading frame, which is translated into a polyprotein that is post-translationally cleaved by three virus-encoded proteases into 10 functional proteins. Several of these potyviral proteins, including nuclear inclusion protein b (NIb), are multifunctional. Here, using the classic GFP silencing in Nicotiana benthamiana gfp-transgenic plants, we show that potato virus Y (PVY) NIb, in addition to its canonical role as the viral RNA-dependent RNA polymerase (RdRP), functions as a suppressor of RNA silencing. Mutational analyses reveal a previously unreported NIb nuclear localization signal (NLS) consisting of a triple-lysine motif. NIb suppression of RNA silencing activity was lost when the NLS was mutated, suggesting that nuclear localization is required for NIb suppression of RNA silencing activity. Analysis of sequenced GFP siRNAs revealed three reproducible hotspot regions at ≈175 nt, ≈320–330 nt, and a broader 3′-proximal region spanning ≈560–700 nt that contains multiple local maxima. These data show differences in the positional distribution of siRNAs between samples expressing NIb and those expressing NIb^Del3×2, the NIb null mutant that does not suppress RNA silencing. However, the positional distribution of GFP-derived small RNAs across the transgene differed modestly between NIb and NIb^Del3×2, while both treatments showed the same three reproducible hotspot regions. Furthermore, NIb was found to interact with four key RNA silencing pathway proteins—AGO4, HSP70, HSP90, and SGS3. Except for HSP90, each of these proteins showed degradation products that were absent in NIb mutants that did not suppress RNA silencing. These findings support a role for NIb in countering host defense during virus infection. Full article