Search Results (1,820)

Bovine viral diarrhea virus (BVDV) is a major pathogen responsible for significant economic losses in the global cattle industry. The diverse transmission routes and the characteristics of asymptomatic infections make it difficult to contain the spread; there is an urgent need to develop new effective antiviral strategies. Nanobodies (Nbs) have become a promising new type of antiviral agent due to their advantages, including small molecular size, stable structure, high specificity, and ease of production. This study successfully screened a specific nanobody, Nb7, targeting the key functional protein NS5A of BVDV using phage display technology. Furthermore, the nanobody was effectively delivered into Madin–Darby bovine kidney (MDBK) cells by fusing it with the cell-penetrating peptide TAT. The results demonstrate that TAT-Nb7, specifically targeting the non-structural protein NS5A of BVDV, significantly inhibits viral replication in MDBK cells. In conclusion, this study indicates that TAT-Nb7 holds promise as a therapeutic candidate for the prevention and control of BVDV infection. Full article

Sexually transmitted infections, notably herpes simplex virus, remain significant global health concerns. Localized delivery systems that provide sustained antiviral activity at mucosal surfaces offer an attractive alternative to systemic therapies. In this study, we developed electrohydrodynamically deposited coatings utilizing a covalent acyclovir–poly (lactic-co-glycolic acid) (ACV–PLGA) conjugate for potential antiviral functionalization of medical devices. The ACV–PLGA prodrug was synthesized via drug-initiated ring-opening polymerization, yielding a copolymer characterized by FTIR, NMR, GPC, and DSC, with controlled drug loading and biodegradable properties. Systematic optimization of electrospinning and electrospraying parameters enabled the fabrication of both particulate and nanofibrous coatings on silicone ring models. Morphological analysis by SEM demonstrated that polymer concentration, solvent composition, and applied voltage critically governed coating architecture, ranging from microparticle layers to uniform bead-free fibers. In vitro studies revealed morphology-dependent degradation profiles and sustained release of ACV over 56 days. This integrated approach combining covalent prodrug synthesis with tunable electrohydrodynamic deposition offers a promising strategy for long-acting local antiviral prophylaxis via functionalized medical surfaces. Full article

Background/Objective: Dendritic cells (DCs) act as sentinels bridging innate and adaptive immunity, and their functions are strongly influenced by dietary and environmental factors. Phytochemicals such as α-Mangostin (A phytochemical, a xanthone derivative from Garcinia mangostina, known for its anti-inflammatory and antioxidant properties) are widely recognized for their antioxidant and anti-inflammatory effects, but their potential to modulate antiviral pattern recognition pathways remains unclear. This study investigated whether phytochemicals activate retinoic acid–inducible gene I (RIG-I: DDX58, a cytosolic receptor recognizing viral RNA and inducing antiviral responses)–dependent signaling in human monocyte-derived dendritic cells (MoDCs) and affect downstream T cell responses. Methods: MoDCs were generated from peripheral blood and stimulated with selected phytochemicals. RIG-I pathway–related transcripts were quantified by qPCR, and protein expression was assessed by Western blotting, intracellular flow cytometry, and immunofluorescence staining. Functional outcomes were evaluated by co-culturing MoDCs with T cells, followed by phenotypic analysis via flow cytometry and measurement of IFN-γ production by ELISA. Results: α-Mangostin stimulation increased RIG-I (DDX58) mRNA levels in MoDCs and induced time-dependent changes in intracellular protein expression. In co-culture, α-Mangostin–treated MoDCs tended to increase the proportion of OX40⁺ 4-1BB⁺ CD4⁺ T cells, accompanied by a significant elevation of IFN-γ levels in supernatants. Experiments with CpG-ODN (synthetic oligodeoxynucleotides mimicking bacterial DNA that activate TLR9) suggested context-dependent crosstalk between the TLR9 and RIG-I signaling axes. Conclusions: Phytochemicals, exemplified by α-Mangostin, prime antiviral responses in human DCs through upregulation of RIG-I and promote Th1-dependent immune responses. These findings suggest that phytochemicals may represent promising nutritional strategies to enhance antiviral immunity while mitigating excessive inflammation under infectious conditions. Full article

The COVID-19 pandemic caused by the SARS-CoV-2 virus has exposed the urgency of research on rapid and efficient virus detection and strategies to inhibit its replication. Previous studies have mostly focused on traditional immunoassay or optical methods, but they have limitations in terms of sensitivity, timeliness, and in-depth analysis of molecular interaction mechanisms. Solid-state nanopore single-molecule detection methods, which can monitor molecular conditions in real time at the single-molecule level, bring new opportunities to solve this problem. The nucleocapsid protein (N protein) of SARS-CoV-2 was systematically investigated under different conditions, such as external drive voltage, pH, nanopore size, and N protein concentration. The translocation of the N protein through the nanopore was then analyzed. Subsequently, we analyzed the translocation characteristics of the N protein, RNA, and N protein–RNA complexes. With the aid of EMSA experiments, we conclusively confirmed that RNA binds to the N protein. Building on this finding, we further explored small molecules that could affect the nanopore translocation of N protein–RNA complexes, such as gallocatechin gallate (GCG), epigallocatechin gallate (EGCG), and the influenza A viral inhibitor Nucleozin. The results show that GCG can disrupt the liquid-phase condensation of the N protein–RNA complex and inhibit the replication of the N protein. Meanwhile, the structural isomer EGCG of GCG and the small molecule Nucleozin can also block RNA-triggered N protein liquid–liquid phase separation (LLPS). Our results confirmed that GCG, EGCG, and Nucleozin exhibit antagonistic effects on the N protein, with differences in their effective concentrations and the potency of their antagonism. Herein, using solid-state nanopore single-molecule detection technology, we developed an experimental method that can effectively detect RNA-induced changes in N protein properties and the regulatory effects of small molecules on the LLPS of N protein–RNA complexes. These findings not only provide highly valuable insights for in-depth research on the molecular interactions involved in viral replication, but also open up promising new avenues for future responses to similar viral outbreaks, the development of a rapid and effective detection method based on solid-state nanopores and single-molecule detection, and antiviral therapies targeting N protein–RNA interactions. Full article

Chikungunya virus (CHIKV) infection during pregnancy represents an increasing public health concern, especially in endemic and epidemic regions. The main concern is vertical transmission, particularly during the peripartum period, which can lead to severe neonatal outcomes such as encephalopathy, hematologic abnormalities, and long-term neurodevelopmental impairment. This review synthesizes current knowledge on pathophysiology, clinical manifestations, diagnosis, maternal and neonatal outcomes, and management of CHIKV infection in pregnancy. Diagnosis relies on clinical evaluation supported by laboratory confirmation, RT-PCR in the acute phase and IgM serology thereafter. Treatment is supportive, using acetaminophen as first-line therapy and corticosteroids for selected refractory cases. No antivirals or vaccines are approved for use in pregnancy as of 2025. Prevention is centered on vector control, personal protection, and epidemiological surveillance. Delivery planning and neonatal monitoring are essential when infection occurs close to term due to the high risk of peripartum transmission. Despite growing recognition of CHIKV’s maternal–fetal impact, significant gaps remain regarding long-term outcomes and optimal management strategies. Strengthening prenatal care, neonatal preparedness, and surveillance systems is crucial to mitigate adverse outcomes and inform future clinical and public health policies. Full article

The phylum Nematoda is host to a vast and diverse virosphere, yet severe viral diseases are rarely observed. This paradox between pervasive infection and limited pathology suggests the existence of a highly effective host–virus “truce”. In this review, we argue that this truce is not a result of viral attenuation but is actively arbitrated by a multi-tiered host immune network, whose primary characteristic is not destructive power but exquisite cost–benefit management. We deconstruct this network into two functional tiers. The first, the “effector layer”, comprises a diverse arsenal of antiviral pathways, including RNA interference (RNAi), the Intracellular Pathogen Response (IPR), and other direct-acting mechanisms. The second, the “regulatory layer”, acts as a command hub, integrating internal physiological states—such as metabolism and aging—with external threat signals to orchestrate a proportional defense, thereby mitigating the high fitness costs of immunity. Understanding this intricate network is critical, as it not only explains the dynamics of infection within nematodes but also has profound implications for a broader medical landscape, particularly through the “Trojan Horse” effect, where nematode-borne viruses might elicit immune responses in their final vertebrate hosts. Together, these insights provide a unified framework for studying nematode–virus interactions and for comparing antiviral strategies across metazoans. Full article

Chronic hepatitis B virus (HBV) infection is a major health problem that leads to approximately one million deaths every year worldwide. Mother-to-child transmission (MTCT) is the major cause of chronic HBV infection. HBV e antigen (HBeAg) is a secretory viral protein and modulates the immunological landscape of the newborn to promote HBV persistence. HBeAg actively reprograms innate and adaptive immunity. Mechanistically, HBeAg regulates macrophage polarization, suppresses dendritic cell and natural killer (NK) cell activities, impairs T cell and B cell functions, and promotes the expansion of myeloid-derived suppressor cells (MDSCs). These multifaceted effects contribute to immune tolerance and persistent HBV infection in the offspring of carrier mothers. Clinically, HBeAg status is a critical determinant for MTCT risk stratification and intervention, particularly in resource-limited settings. Despite advances in neonatal immunoprophylaxis and maternal antiviral therapy, residual transmission of HBV persists. Emerging approaches targeting HBeAg directly or restoring antiviral immunity offer promising avenues for breaking immune tolerance and achieving HBV elimination. This review summarizes current understanding of HBeAg-mediated immune modulation and highlights strategies that are being used to disrupt MTCT and treat HBV patients. Full article

West Nile Virus (WNV), a mosquito-borne flavivirus first identified in Uganda in 1937, has emerged over the past quarter century as a major global public health threat. Since its introduction into North America in 1999, WNV has become the leading cause of arboviral neuroinvasive disease, with recurrent outbreaks continuing across Europe, Africa, and the Americas. This review provides a comprehensive overview of the microbiology, epidemiology, and clinical impact of WNV. We discuss the molecular biology of the virus, highlighting its genomic organization, replication strategies, and the structural and non-structural proteins that underpin viral pathogenesis and immune evasion. The complex enzootic transmission cycle, involving Culex mosquitoes and diverse avian reservoir hosts, is examined alongside ecological and climatic determinants of viral amplification and spillover into humans and equines. The clinical spectrum of WNV infection is outlined, ranging from asymptomatic seroconversion to West Nile fever and life-threatening neuroinvasive disease, with particular emphasis on risk factors for severe outcomes in older and immunocompromised individuals. Current approaches to diagnosis, supportive management, and vector control are critically reviewed, while challenges in vaccine development and the absence of effective antiviral therapy are underscored. Finally, we address future research priorities, including therapeutic innovation, predictive outbreak modeling, and genomic surveillance of viral evolution. WNV exemplifies the dynamics of emerging zoonotic diseases, and its persistence underscores the necessity of a coordinated One Health approach integrating human, animal, and environmental health. Continued scientific advances and public health commitment remain essential to mitigate its enduring global impact. Full article

Artificial intelligence (AI) is increasingly transforming biomedical research and patient care by integrating complex biological, radiological, and healthcare information. In the field of viral respiratory infections, AI-driven approaches have shown great promise in elucidating the complexity of lung immune responses and the dynamic interplay between host and pathogen. Applications include predicting cytokine storm and acute respiratory distress syndrome (ARDS), integrating imaging findings with immunological and laboratory data, and identifying molecular and cellular signatures through single-cell and multi-omics analyses. Similar methodologies have been applied to influenza and respiratory syncytial virus (RSV), providing insights into the mechanisms distinguishing protective from maladaptive pulmonary immunity. This narrative review summarizes current evidence on how AI can evolve into a form of translational intelligence, capable of bridging mechanistic immunology with clinical application. The review explores AI-based models for disease severity prediction, patient stratification, and therapeutic response assessment, as well as emerging approaches in drug repurposing and vaccine response prediction. By integrating biological complexity with clinical context, AI offers new opportunities to uncover immune signatures predictive of antiviral or immunomodulatory efficacy and to guide personalized management strategies. Full article

Viruses account for the most abundant biological entities in the biosphere and can be either symbiotic or pathogenic. While pathogenic viruses have developed strategies to evade immunity, the host immune system has evolved overlapping and redundant defenses to sense and fight viral infections. Nutrition and metabolic needs sculpt viral–host interactions and determine the course and outcomes of the infection. In this review, we focus on the hexosamine biosynthesis pathway (HBP), a nutrient-sensing pathway that controls immune responses and host–viral interactions. The HBP converges on O-GlcNAcylation, a dynamic post-translational modification of cellular proteins, that emerged as a critical effector of immune cell development, differentiation, and effector functions. We present a broad overview of uncovered O-GlcNAc substrates identified in the context of viral infections and with a functional impact on antiviral immunity and viral restriction, or conversely on exacerbating viral-induced pathologic inflammation or viral oncogenesis. We discuss the clinical implications of these findings, current limitations, and future perspectives to harness this pathway for therapeutic purposes. Full article

BK polyomavirus (BKPyV) causes severe urinary tract diseases, including BKPyV-associated nephropathy (BKPyVN) and ureteric stenosis, in immunocompromised individuals such as renal transplant recipients. Effective antiviral therapies for BKPyV infection remain an unmet clinical need. While the interferon-stimulated gene 20 (ISG20) exhibits broad-spectrum antiviral activity against RNA viruses, its role and mechanisms against DNA viruses are poorly defined. This study demonstrates, for the first time, potent antiviral activity of ISG20 against BKPyV. This restriction was observed with both endogenous levels of ISG20 and upon overexpression, and this effect was confirmed by ISG20 knockout and immunofluorescence imaging. We observed that ISG20 expression is dynamically regulated during BKPyV infection: it is upregulated both during early infection and by expression of the viral large T antigen (LT) alone. However, endogenous ISG20 expression becomes significantly suppressed during later stages of infection, coinciding with declining LT levels. The physical interaction between LT and both wild-type and mutant ISG20 suggests a potential viral strategy to sequester this restriction factor. These findings establish ISG20 as a novel host restriction factor against BKPyV and suggest that BKPyV employs LT-mediated mechanisms to evade or counteract ISG20’s antiviral effects. Our results elucidate a complex biphasic interplay between BKPyV and host innate immunity, identifying ISG20 as a potential therapeutic target for BKPyV-associated diseases. Full article

Zika virus (ZIKV) caused Zika outbreaks and continues to post threats to public health. ZIKV infection may cause congenital abnormalities during pregnancy and neurological manifestations in adults. The recurrent public health threat of Zika in various geographical areas demonstrates a need for the development of effective therapeutics. Currently, there are no approved therapies for Zika. ZIKV is a single-stranded, positive-sense RNA virus, whose genome encodes three structural proteins and seven non-structural proteins. The surface envelope (E) protein is essential for host–cell recognition and viral entry; therefore, inhibition of E-mediated viral entry is a key strategy underlying antiviral treatments. Here, molecular docking-based virtual screening was used to screen small-molecule compound libraries to identify potential ZIKV entry inhibitors. Among the compounds identified, Pyrimidine-Der1 exhibited efficient inhibition of reporter ZIKV infection. The microscale thermophoresis assay confirmed its binding with the ZIKV E protein. This compound has effective inhibition of authentic ZIKV infection in a plaque inhibition assay against R103451, PAN2016, and FLR human strains (IC₅₀: ~3–5 μM). Additionally, it efficiently inhibited ZIKV infection at viral entry and fusion steps of the virus life cycle in a time-of-addition assay. Overall, Pyrimidine-Der1 is a promising ZIKV entry inhibitor, warranting further optimization and evaluation. Full article

Background: In recent decades, research on Hepatitis C Virus (HCV) drug-resistant variants has expanded; however, critical gaps remain in our understanding of global contributions, emerging trends, and future research directions. Here, we present a bibliometric analysis to understand the research themes and trends in research related to HCV drug-resistant variants published between 1999 and 2025. Methods: Publications related to HCV drug-resistant variants published between 1999 and 2025 were searched on the Web of Science and Scopus databases. Publication metadata and content-based data were extracted and analyzed using Bibliometrix and VOSviewer for keyword co-occurrence plot and cluster analysis. Results: The analysis of 653 articles revealed a clear paradigm shift, driven by the introduction of direct-acting antivirals (DAAs), which led to a significant surge in annual publications, peaking between 2014 and 2018. This shift in focus led to an emphasis on DAA efficacy, resistance mechanisms, and advanced genotyping. The United States was the most productive country, with the highest number of publications (n = 134) and citations (n = 6458). The University of São Paulo was the most productive institution (n = 40), while Antimicrobial Agents and Chemotherapy published the highest number of articles in this field (n = 40). Susser S. was the most productive researcher. Collaboration networks were found to be predominantly centered in high-income countries. Analysis of studies on minority variants showed that most studies originated from Europe and the United States, identifying low-frequency resistance-associated substitutions (RASs) such as A156V, D168V, Y93H, and S282T, with prevalence ranging from <1% to 35%, which were frequently associated with viral breakthrough and reduced treatment response. Conclusions: The field successfully transitioned to the DAA era, but research output and collaboration networks were primarily driven by high-income countries, leaving a critical gap in data from Low- and Middle-Income Countries (LMICs). Closing this gap by integrating LMIC data is the next essential step to ensure global elimination strategies are effective for all countries from different income strata. Full article

Andrographis paniculata, a medicinal plant widely found in Asia, contains andrographolide as its main active compound, known for its wide-ranging pharmacological effects, including anti-inflammatory, anti-cancer, anti-obesity, and anti-diabetic properties. Recent investigations have highlighted the anti-infective potential of andrographolide and its derivatives, with demonstrated antiviral, antibacterial, and antimalarial activities. This review summarizes progress in andrographolide’s anti-infective applications, focusing on its structure–activity relationship (SAR) and mechanisms of action. Researchers have used semi-synthetic methods, such as esterification, oxidation, Michael addition, salification, and hybrid design, to enhance andrographolide’s physicochemical properties and biological activity. These derivatives show potent antiviral activity against RNA and DNA viruses, antibacterial activity against Gram-positive and Gram-negative bacteria, antifungal effects, and antiparasitic activity against Plasmodium spp. and Leishmania spp. Nevertheless, poor solubility and limited bioavailability still hinder their clinical translation. Strategies such as nano delivery systems and β-cyclodextrin complexes are discussed to improve bioavailability. Although andrographolide itself has not received regulatory approval as a stand-alone drug, several andrographolide-containing preparations have been clinically used in certain countries. Overall, this review brings together evidence on antiviral, antibacterial, antifungal, and antiparasitic activities, linking them with structure–activity trends and pharmacokinetic insights, thereby providing a consolidated foundation for future development and clinical translation. Full article

Human adenovirus infections are typically self-limiting but can become life-threatening in pediatric populations and immunocompromised individuals. Despite this clinical importance, efforts to develop antiviral drugs against adenoviruses remain limited. A promising strategy is to target the adenovirus protease (AVP), an enzyme essential for viral maturation and infectivity. Yet, research on AVP has lagged far behind that on other viral proteases. In this work, we aimed to reposition AVP as a viable target for antiviral therapy. We first discuss why AVP research has fallen behind and emphasize the need to redirect attention toward this protease. Building on advances in SARS-CoV-2 drug discovery, we evaluated the potential of repurposing inhibitors of the main protease (M^pro) and papain-like protease (PL^pro) as modulators of AVP. Additionally, we examined the untapped potential of phytochemicals as novel scaffolds. These analyses were supported by original molecular docking studies. Our results revealed that previously reported SARS-CoV-2 inhibitors, such as the M^pro inhibitor ensitrelvir and the PL^pro inhibitor (compound) 19, engage the catalytic site of AVP and may serve as starting scaffolds for inhibitor design. Screening of phytochemicals further identified promising candidates, including apigenin, camptothecin, kaempferol, and piperine. Together, these findings highlight AVP’s druggability and suggest that both repurposed antivirals and natural products provide complementary avenues for inhibitor development. Finally, we provide some recommendations to facilitate efforts in the discovery of novel AVP inhibitors. Full article