Search Results (2,002)

Viral outbreaks have caused significant mortality and economic losses in aquaculture, highlighting the urgent need for effective therapies and a deeper understanding of antiviral and immune mechanisms in key species. This study investigates the constitutive and virus-induced antiviral responses in juvenile rainbow trout (Oncorhynchus mykiss) following infection with viral hemorrhagic septicemia virus (VHSV). Trout (30 g) were infected by immersion with VHSV (TCID₅₀ = 10⁵ mL⁻¹) for two hours. Samples were collected at 24, 72, and 120 h post-infection to assess hematology, innate immunity, viral load, and transcriptomic response. At 24 h post-infection, no immune response or increase in viral load was detected, suggesting the host had not yet recognized the virus and was still in the incubation phase. By 72 h, viral replication peaked, with high viral loads observed in mucosal tissues (skin and gills) and immune organs (kidney, spleen, liver), alongside strong up-regulation of antiviral genes, such as viperin. This gene maintained high expression through the final sampling point, indicating its key role in the antiviral response. At this stage, reduced immune competence was observed, marked by elevated nitric oxide and circulating thrombocytes. At 120 h, modest increases in peripheral monocyte, plasma lysozyme, and peroxidase activity were detected; however, these responses were insufficient to reduce viral load, suggesting the resolution phase had not yet begun. In summary, while a limited immune response was observed by the end of the trial, the consistent antiviral activity of viperin from peak infection to 120 h post-infection underscores its importance in the defence against VHSV in rainbow trout. Full article

The development of severe SARS-CoV-2 pneumonia is characterized by extensive lung inflammation, which, in turn, leads to respiratory distress and a decline in blood oxygen levels. Hospital admission, along with intensive care or ventilator usage, becomes necessary because this condition leads to serious respiratory problems. This review aims to provide a comprehensive overview of the pathophysiological mechanisms, diagnostic methods, and current therapeutic options for pneumonia caused by the SARS-CoV-2 virus. The pathophysiological process of severe pneumonia due to SARS-CoV-2 infection is characterized by direct lung damage from viral replication, an excessive immune system response, inflammation, impaired gas exchange, and multi-organ failure. The coexistence of various medical conditions leads to substantial lung impairment, resulting in hypoxia and respiratory failure, which can ultimately lead to fatal outcomes. The diagnosis of severe SARS-CoV-2 pneumonia is made through a combination of clinical, radiologic, and laboratory findings. A multifaceted approach integrating antiviral therapy, corticosteroids, oxygen supplementation, ventilatory management, and immunomodulation is imperative to control inflammation and enhance clinical outcomes. Early intervention, meticulous monitoring, and personalized care are paramount for enhancing survival and mitigating complications in critically ill patients with COVID-19 pneumonia. Full article

Since the onset of the COVID-19 pandemic, remarkable progress has been made in the development of antiviral therapies for SARS-CoV-2. Several direct-acting antivirals, such as remdesivir, molnupiravir, and nirmatrelvir/ritonavir, offer clinical benefits. These agents have significantly contributed to reducing the viral loads and duration of the illness, as well as the disease’s severity and mortality. However, despite these advances, important limitations remain. The continued emergence of resistant SARS-CoV-2 variants highlights the urgent need for adaptable and durable therapeutic strategies. Therefore, this review aims to provide an updated overview of the main antiviral strategies that are used and the discovery of new drugs against SARS-CoV-2, as well as the therapeutic limitations that have shaped clinical management in recent years. The major challenges include resistance associated with viral mutations, limited treatment windows, and unequal access to treatment. Moreover, there is an ongoing need to identify novel compounds with broad-spectrum activity, improved pharmacokinetics, and suitable safety profiles. Combination treatment regimens represent a promising strategy to increase the efficacy of treating COVID-19 while minimizing the potential for resistance. Ideally, these interventions should be safe, affordable, and easy to administer, which would ensure broad global access and equitable treatment and enable control of COVID-19 cases and preparedness for future threats. Full article

Polyomaviruses are a family of small DNA viruses capable of establishing persistent infections, and they can pose significant pathogenic risks in immunocompromised hosts. While traditionally studied in the context of viral reactivation and immune suppression, recent evidence has highlighted the gut microbiota as a critical regulator of host immunity and viral pathogenesis. This review examines the complex interactions between polyomaviruses, the immune system, and intestinal microbiota, emphasizing the role of short-chain fatty acids (SCFAs) in modulating antiviral responses. We explore how dysbiosis may facilitate viral replication, reactivation, and immune escape and also consider how polyomavirus infection can, in turn, alter microbial composition. Particular attention is given to the Firmicutes/Bacteroidetes ratio as a potential biomarker of infection risk and immune status. Therapeutic strategies targeting the microbiota, including prebiotics, probiotics, and fecal microbiota transplantation (FMT), are discussed as innovative adjuncts to immune-based therapies. Understanding these tri-directional interactions may offer new avenues for mitigating disease severity and improving patient outcomes during viral reactivation. Full article

Background: BK polyomavirus (BKPyV) reactivation is a common complication after kidney transplantation and may result in nephropathy and graft loss. As there is no effective antiviral therapy, management focuses on early detection and reduction of immunosuppression, which increases the risk of rejection. Identifying patients at higher risk remains challenging. Monitoring BKPyV-specific T-cell responses could aid in predicting reactivation. This study evaluated the usefulness of ELISpot to monitor BKPyV-specific cellular immunity before and after kidney transplantation. Methods: A prospective multicenter study was conducted between October 2020 and March 2022. ELISpot assays were performed prior to transplantation and two months afterward. Results: Seventy-two patients were included, with a median age of 56 years; 61% were men, and 24% had undergone previous transplantation. Nine patients developed presumptive BKPyV-nephropathy. No significant differences were found in donor type, induction therapy, or rejection rates between patients with or without nephropathy (p = 0.38). Based on ELISpot results, patients were classified into three groups according to their risk of BKPyV-nephropathy. The high-risk group included those who changed from positive to negative at 2 months post-transplant, representing 40% of presumptive BKPyV-nephropathy cases. Patients who remained negative at 2 months were classified as moderate risk (14.5%), while those with a positive ELISpot at 2 months comprised the low-risk group (0%). In the logistic regression analysis, both the ELISpot risk category [OR 19 (CI 1.7–2.08)] and the use of mTOR inhibitors from the start of transplantation [OR 0.02 (CI 0.01–0.46)] were significantly associated with BKPyV-nephropathy. Conclusions: Monitoring BKPyV-specific T cells with ELISpot before and after kidney transplantation may help stratify patients by risk of reactivation. Loss of BKPyV immunity at two months is associated with nephropathy, while mTOR-based immunosuppression appears protective. This strategy could guide personalized immunosuppression and surveillance. Full article

Cirrhosis remains a significant global health burden, responsible for nearly 4% of annual deaths worldwide. Despite progress in antiviral therapies and public health measures, its prevalence has plateaued, particularly in regions affected by viral hepatitis, alcohol misuse, and metabolic syndrome. This review presents a comprehensive synthesis of the multifactorial drivers of cirrhosis, including hepatocyte injury, liver stellate cell activation, and immune-mediated inflammation. The emphasis is on the central role of metabolic dysfunction, characterized by mitochondrial impairment, altered lipid and glucose metabolism, hormonal imbalance, and systemic inflammation, in exacerbating disease progression. While current therapies may slow the progression of early-stage disease, they are very often ineffective in reversing established fibrosis. Emerging molecular strategies offer promising alternatives by targeting key pathogenic pathways. These include AMPK activators (e.g., metformin, AICAR), FGF21 analogs, and mitochondria-targeted agents (e.g., MitoQ, urolithin A, NAD+ precursors) to restore bioenergetic balance and reduce oxidative stress. Other approaches, such as mesenchymal stem cell therapy, inflammasome inhibition, and hormonal modulation, aim to suppress fibrogenesis and restore liver homeostasis. The integration of systems biology and multi-omics profiling supports patient stratification and precision medicine. This review highlights a shift toward mechanism-based interventions that have the potential to alter cirrhosis outcomes and improve patient survival. Full article

RNA viruses pose significant threats to global health, causing diseases such as COVID-19, HIV/AIDS, influenza, and dengue. These viruses are characterized by high mutation rates, rapid evolution, and the ability to evade traditional antiviral therapies, making effective treatment and prevention particularly challenging. In recent years, CRISPR/Cas13 has emerged as a promising antiviral tool due to its ability to specifically target and degrade viral RNA. Unlike conventional antiviral strategies, Cas13 functions at the RNA level, providing a broad-spectrum and programmable approach to combating RNA viruses. Its flexibility allows for rapid adaptation of guide RNAs to counteract emerging viral variants, making it particularly suitable for highly diverse viruses such as SARS-CoV-2 and HIV. This review discusses up-to-date applications of Cas13 in targeting a wide range of RNA viruses, including SARS-CoV-2, HIV, dengue, influenza, and other RNA viruses, focusing on its therapeutic potential. Preclinical studies have demonstrated Cas13’s efficacy in degrading viral RNA and inhibiting replication, with applications spanning prophylactic interventions to post-infection treatments. However, challenges such as collateral cleavage, inefficient delivery, potential immunogenicity, and the development of an appropriate ethical framework must be addressed before clinical translation. Future research should focus on optimizing crRNA design, improving delivery systems, and conducting rigorous preclinical evaluations to enhance specificity, safety, and therapeutic efficacy. With continued advancements, Cas13 holds great promise as a revolutionary antiviral strategy, offering novel solutions to combat some of the world’s most persistent viral threats. Full article

Viral infections persistently challenge global health through immune evasion and zoonotic transmission. Dendritic cells (DCs) play a central role in antiviral immunity by detecting viral nucleic acids via conserved pattern recognition receptors, triggering interferon-driven innate responses and cross-presentation-mediated activation of cytotoxic CD8⁺ T cells. This study synthesizes DC-centric defense mechanisms against viral subversion, encompassing divergent nucleic acid sensing pathways for zoonotic DNA and RNA viruses, viral counterstrategies targeting DC maturation and interferon signaling, and functional specialization of DC subsets in immune coordination. Despite advances in DC-based vaccine platforms, clinical translation is hindered by cellular heterogeneity, immunosuppressive microenvironments, and limitations in antigen delivery. Future research should aim to enhance the efficiency of DC-mediated immunity, thereby establishing a robust scientific foundation for the development of next-generation vaccines and antiviral therapies. A more in-depth exploration of DC functions and regulatory mechanisms may unlock novel strategies for antiviral intervention, ultimately paving the way for improved prevention and treatment of viral infections. Full article

Nanoparticles (NPs) synthesised through biogenic routes have emerged as a sustainable and innovative platform for biomedical applications such as antibacterial, anticancer, antiviral, anti-inflammatory, drug delivery, wound healing, and imaging diagnostics. Among these, silver nanoparticles (AgNPs) have attracted significant attention due to their unique physicochemical properties and therapeutic potential. This review examines the biogenic synthesis of AgNPs, focusing on microbial, plant-based, and biomolecule-assisted approaches. It highlights how reaction conditions, such as pH, temperature, and media composition, influence nanoparticle size, shape, and functionality. Particular emphasis is placed on microbial synthesis for its eco-friendly and scalable nature. The mechanisms of AgNP formation and their structural impact on biomedical performance are discussed. Key applications are examined including antimicrobial therapies, cancer treatment, drug delivery, and theranostics. Finally, the review addresses current challenges, such as reproducibility, scalability, morphological control, and biosafety, and outlines future directions for engineering AgNPs with tailored properties, paving the way for sustainable and effective next-generation biomedical solutions. Full article

We report a case of herpes simplex virus type 1 (HSV-1) anterior uveitis evolving into an acute iris transillumination-like syndrome with secondary pigmentary glaucoma, highlighting diagnostic challenges and treatment considerations. A 61-year-old immunocompetent woman presented with unilateral anterior uveitis characterized by keratic precipitates and mild anterior chamber inflammation. The condition was initially treated with topical and subconjunctival corticosteroids without antiviral therapy. After an initial resolution of symptoms, upon the cessation of treatment, the patient developed features resembling unilateral acute iris transillumination (UAIT) syndrome with elevated intraocular pressure, diffuse pigment dispersion, and progressive iris transillumination defects. Aqueous polymerase chain reaction (PCR) testing confirmed the presence of HSV-1. Despite the initiation of antiviral therapy, the condition progressed to severe pigmentary glaucoma, with unreliable intraocular pressure measurements due to prior LASIK surgery. Cataract extraction, pars plana vitrectomy, and Ahmed valve implantation were performed, with only partial recovery of visual acuity. This case illustrates that HSV-1 uveitis can mimic or transition into a UAIT-like syndrome, possibly due to steroid use without concurrent antiviral treatment, which may exacerbate viral replication and damage to the iris pigment epithelium. Aqueous PCR testing aids in differential diagnosis, but indicative medical history and clinical findings should remain instrumental. Clinicians should maintain a high index of suspicion for herpetic etiology in anterior uveitis cases and initiate prompt antiviral treatment to prevent potentially sight-threatening complications. Full article

The scientific community’s interest in natural compounds with antiviral properties has considerably increased after the emergence of the severe acute respiratory syndrome coronavirus (SARS-CoV-2), especially for their potential use in the treatment of the COVID-19 infection. From this perspective, bovine coronavirus (BCoV), member of the genus β-CoV, represents a valuable virus model to study human β-CoVs, bypassing the risks of handling highly pathogenic and contagious viruses. Pimarane diterpenes are a significant group of secondary metabolites produced by phytopathogenic fungi, including several Diplodia species. Among the members of this class of natural products, sphaeropsidin A (SphA) and its analog sphaeropsidin B (SphB) are well known for their bioactivities, such as antimicrobial, insecticidal, herbicidal, and anticancer. In this study, the antiviral effects of SphA and SphB were evaluated for the first time on bovine (MDBK) cells infected with BCoV. Our findings showed that both sphaeropsidins significantly increased cell viability in infected cells. These substances also caused substantial declines in the virus yield and in the levels of the viral spike S protein. Interestingly, during the treatment, a cellular defense mechanism was detected in the downregulation of the aryl hydrocarbon receptor (AhR) signaling, which is affected by BCoV infection. We also observed that the presence of SphA and SphB determined the deacidification of the lysosomal environment in infected cells, which may be related to their antiviral activities. In addition, in silico investigations have been performed to elucidate the molecular mechanism governing the recognition of bovine AhR (bAhR) by Sphs. Molecular docking studies revealed significant insights into the structural determinants driving the bAhR binding by the examined compounds. Hence, in vitro and in silico results demonstrated that SphA and SphB are promising drug candidates for the development of efficient therapies able to fight a β-CoV-like BCoV during infection. Full article

The enterovirus Coxsackievirus B3 causes a range of serious health problems, including aseptic meningitis, myocarditis, and pancreatitis. Currently, Coxsackievirus B3 has no targeted antiviral treatments or vaccines, leaving supportive care as the primary management option. Understanding how Coxsackievirus B3 interacts with and alters the blood–brain barrier may help identify new therapies to combat this often-devastating infection. We reanalyzed a previously published RNA sequencing dataset for Coxsackievirus B3-infected human-induced pluripotent stem-cell-derived brain endothelial cells (iBECs) to examine how Coxsackievirus B3 altered mRNA expression. By integrating GSEA, EnrichR, and iLINCs-based perturbagen analysis, we present a novel, systems-level approach to uncover potential drug repurposing candidates for CVB3 infection. We found dynamic changes in host transcriptomic response to Coxsackievirus B3 infection at 2- and 5-day infection time points. Downregulated pathways included ribosomal biogenesis and protein synthesis, while upregulated pathways included a defense response to viruses, and interferon production. Using iLINCs transcriptomic analysis, MEK, PDGFR, and VEGF inhibitors were identified as possible novel antiviral therapeutics. Our findings further elucidate Coxsackievirus B3-associated pathways in (iBECs) and highlight potential drug repurposing candidates, including pelitinib and neratinib, which may disrupt Coxsackievirus B3 pathology at the blood–brain barrier (BBB). Full article

Viral conjunctivitis is a highly contagious ocular condition that significantly impacts patient quality of life and healthcare resources. Despite its self-limiting nature, the condition remains a significant public health concern due to its high transmissibility, prolonged symptoms, and potential complications such as subepithelial infiltrates (SEIs). This review aimed to synthesize and evaluate current management strategies for adenoviral conjunctivitis and provide an evidence-based treatment framework. A systematic literature search of PubMed and the Cochrane Library was conducted, identifying 25 eligible studies published between 2009 and 2024 that focused on clinical interventions including supportive care, antiseptics, corticosteroids, antivirals, and immune modulators. The findings indicate that while supportive therapy and hygiene measures remain central to care, antiseptic agents, specifically povidone–iodine, and topical steroids offer additional benefit in reducing symptom duration and complications. Combination therapies integrating antiseptics, corticosteroids, and immunomodulators show promise for more severe cases, especially those complicated by SEIs. This review proposes an evidence-based comprehensive, multimodal approach management algorithm while highlighting the need for future research in antiviral development and diagnostic innovation to avoid mistreatment and unnecessary antibiotic use. Full article

Background: Cytomegalovirus (CMV) colitis is commonly seen in patients who are immunodeficient or have inflammatory bowel disease. Among the gastrointestinal sites affected by CMV, the colon is the most frequently affected, though rectal involvement is relatively rare. Reactivated CMV proctitis primarily occurs in elderly patients with comorbidities and is quite uncommon in immunocompetent individuals. Patients with reactivated CMV typically present with symptoms such as diarrhea, hematochezia, or tenesmus. Case presentation: We report a case of a female patient with uncontrolled diabetes who presented to the clinic complaining of perianal pain. She had no history of diarrhea or rectal bleeding. Lower GI endoscopy reported a small, localized, approximately 0.5 cm swelling in the proximal anal canal in addition to sigmoid diverticulosis. The biopsy revealed a small ulcer at the anorectal junction caused by CMV and confirmed by immunohistochemistry. Unfortunately, the patient was lost to follow-up before antiviral therapy could be initiated. Conclusions: This case highlights an uncommon presentation of reactivated CMV proctitis in an older diabetic patient presenting solely with perianal pain. Clinicians should maintain a high index of suspicion for CMV infection in elderly patients with comorbidities, even when classical colitis symptoms are absent, to avoid delayed diagnosis and management. Full article

Kyasanur Forest disease virus (KFDV), a tick-borne Orthoflavivirus endemic to the Indian subcontinent, is a public health threat due to its recurrent outbreaks and expanding geographic range. This review provides a comprehensive overview of KFDV, encompassing its epidemiological trends, transmission dynamics, and ecological determinants that influence its spread. We delve into the current understanding of KFDV pathogenesis, highlighting key viral and host factors that drive infection and disease progression. Despite the absence of targeted antiviral therapies, recent advances have spurred the development of candidate therapeutics, including broad-spectrum antivirals and immunomodulators. We also discuss progress in vaccine development, with an emphasis on the limitations of the existing formalin-inactivated vaccine and the promise of next-generation platforms. Furthermore, we explore recent innovations in diagnostics, including molecular and serological tools, that aim to improve early detection and surveillance. A multidisciplinary approach integrating virology, immunology, ecology, and public health is essential for the effective management and eventual control of KFDV outbreaks. Full article