Search Results (5,353)

In this work, we synthesized a small library of tricyclic compounds to assess whether they might have both anticancer and antiviral activity against three viruses that have recently caused epidemics. Concerning their anti-tumour activity, derivative 1 was found to be the compound with the highest GI₅₀ values on some cancer cell line panels. Particularly, in melanoma cell lines, its GI₅₀ values ranged between 1.54 μM (MALME-3M) and 2.03 μM (M14). Several derivatives with considerable anti-tumour activity showed antiviral activity as well, against influenza A virus (e.g., derivative 19, selectivity index of 21.36 in MDCK cells) or against Zika virus (compound 13, selectivity index of 20.20 in Huh-7 cells). Moreover, compounds 13 and 12 showed anti-SARS-CoV-2 activity, with selectivity indices of 150.00 and 63.63, respectively. Compound 1, for its anticancer activity, and 13, for its anti-SARS-CoV-2 activity, together with the compounds active against Zika virus and influenza A virus, are promising candidates for further studies. Full article

Interferons (IFNs) are key cytokines at the intersection of innate and adaptive immunity. While their antiviral and antitumor roles are well recognized, emerging evidence implicates IFNs—particularly types I, II, and III—in the initiation and progression of autoimmune diseases (ADs). This review synthesizes current data on IFN biology, their immunoregulatory and pathogenic mechanisms, and their contributions to distinct AD phenotypes. We conducted a comprehensive review of peer-reviewed literature on IFNs and autoimmune diseases, focusing on publications indexed in PubMed and Scopus. Studies on molecular pathways, immune cell interactions, disease-specific IFN signatures, and clinical correlations were included. Data were extracted and thematically organized by IFN type, signaling pathway, and disease context, with emphasis on rheumatic and systemic autoimmune disorders. Across systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, systemic sclerosis, idiopathic inflammatory myopathies, multiple sclerosis, type 1 diabetes, psoriasis, and inflammatory bowel diseases, IFNs were consistently associated with aberrant activation of pattern recognition receptors, sustained expression of interferon-stimulated genes (ISGs), and dysregulated T cell and B cell responses. Type I IFNs often preceded clinical onset, suggesting a triggering role, whereas type II and III IFNs modulated disease course and severity. Notably, IFNs exhibited dual immunostimulatory and immunosuppressive effects, contingent on tissue context, cytokine milieu, and disease stage. IFNs are central mediators in autoimmune pathogenesis, functioning as both initiators and amplifiers of chronic inflammation. Deciphering the context-dependent effects of IFN signaling may inform targeted therapeutic strategies and advance precision immunomodulation in autoimmune diseases. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) closely interacts with host cellular mechanisms, with mitochondria playing a crucial role in this process. As essential organelles that control cellular energy production, apoptosis, reactive oxygen species (ROS) metabolism, and innate immune responses, mitochondria are vital to the development of COVID-19. However, the exact molecular interactions between mitochondria and SARS-CoV-2 remain under active investigation. Gaining a comprehensive understanding of mitochondrial involvement in SARS-CoV-2 infection is therefore essential for uncovering complex disease mechanisms, identifying prognostic biomarkers, and developing effective treatments. Ultimately, exploring these virus–host interactions may provide new insights into the fundamental and complex aspects of mitochondrial physiology and pathophysiology. Full article

Foot-and-mouth disease (FMD) is a highly contagious viral infection affecting livestock. Although inactivated vaccines are commonly used, their effectiveness is limited by an immunity gap. Therefore, complementary antiviral strategies are required for effective control and prevention. Lignans, plant-derived compounds, have shown promising antiviral properties, yet their potential against foot-and-mouth disease virus (FMDV) remains underexplored. This study employed virtual screening to identify lignan compounds targeting viral RNA-dependent RNA polymerase (3D^pol). Six lignan compounds were selected for cytotoxicity and antiviral activity evaluation including pre-viral entry, post-viral entry, and protective effect assays. Antiviral activity assay showed that (-)-asarinin and sesamin exhibit potent inhibition effects in the post-viral entry with EC50 of 15.11 μM and 52.98 μM, respectively, using immunoperoxidase monolayer assay. Both compounds exhibited dose-dependent reduction in viral replication with significant suppression of negative-strand RNA production. Lignans’ ability to target FMDV 3D^pol was further confirmed using a cell-based FMDV minigenome assay. Among the tested lignans, (-)-asarinin demonstrated remarkable inhibition of GFP expression (IC50 value at 10.37 μM), while sesamin required a higher concentration for similar effects. In silico prediction revealed that these lignans preferentially bind to FMDV 3D^pol active site. These findings are the first to establish (-)-asarinin and sesamin as promising antiviral candidates against FMDV. Full article

Respiratory viral infections are a major cause of morbidity and mortality worldwide. The COVID-19 pandemic has evidenced the need for broad-spectrum antivirals and improved preclinical models that more accurately recapitulate human respiratory disease. These new strategies should also involve the search for drug targets in the infected cell that hamper the development of resistance and of potential efficacy against diverse viruses. Since many viruses reprogram cellular metabolism to support viral replication, we performed a comparative analysis of inhibitors targeting the PI3K/AKT/mTOR pathway, central to virus-induced metabolic adaptations, using MRC5 lung fibroblasts and Huh7 hepatoma cells. HCoV-229E infection in MRC5 cells caused the expected shift in the energy metabolism but the inhibitors had markedly different effects on the metabolic profile and antiviral activity in these two cell lines. Dichloroacetate (DCA), a clinically approved inhibitor of aerobic glycolysis, showed antiviral activity against HCoV-229E in MRC5 cells, but not in Huh7 cells, underscoring that the screening model is more critical than previously assumed. We further tested DCA in polarized human small airway epithelial cells cultured in air–liquid interface, a 3D model that mimics the human respiratory tract. DCA reduced the viral progeny of HCoV-229E, SARS-CoV-2, and respiratory syncytial virus by 2–3 orders of magnitude, even when administered after infection was established. Our work reinforces the need for advanced human preclinical screening models to identify antivirals that target host metabolic pathways frequently hijacked by respiratory viruses, and establishes DCA as a proof-of-concept candidate. Full article

Background: Pregnancy is a time when women are uniquely engaged with the healthcare system and are often motivated to participate in activities directed toward improvement of their own health and ensuring the health of their unborn child, which also provides an opportunity for healthcare interventions such as treatment for hepatitis C virus (HCV) infection. Methods: This was a multi-site, prospective, open-label, pharmacokinetic (PK) study conducted at two large maternity hospitals in Melbourne, Australia, to evaluate the safety and pharmacokinetics of antenatal sofosbuvir (SOF) and velpatasvir (VEL) treatment administered for 12 weeks during the second and third trimester. Five women were recruited and underwent detailed PK assessments across three visits. Results: Compared to historical data in non-pregnant women, SOF area under the concentration curve (AUC) and maximum concentrations (Cmax) were 60% and 49% higher in pregnancy, respectively. In contrast, exposure to the inactive metabolite of SOF, GS-331007, was 43% lower in pregnancy. Both Cmax and AUC for VEL in pregnancy were similar to values reported in historic non-pregnant women (~21% lower in pregnant women). SOF/VEL was safe and well tolerated. Conclusions: These results add to the limited published experience prescribing antivirals in pregnancy and provide further support for a larger ongoing prospective study and other efforts to support HCV treatment in pregnancy. Full article

The objective of this study was to evaluate the antiviral activity of glucosyl hesperidin (GH), a water-soluble derivative of hesperidin with known antioxidant and anti-inflammatory properties, in order to explore its potential applications. Antiviral activity was assessed using feline calicivirus (FCV), a surrogate model for human norovirus, a major foodborne pathogen. Cytotoxicity testing in Crandell–Rees feline kidney (CRFK) cells demonstrated that GH exhibited high biocompatibility, maintaining 100% cell viability at concentrations up to 8000 μM. Antiviral efficacy assays revealed that GH inhibited FCV replication in a concentration-dependent manner across the range of 250~8000 μM, with a half-maximal inhibitory concentration (IC₅₀) of 3281 μM. Complete viral inhibition, however, was not achieved at the maximum concentration tested. In conclusion, GH was shown to inhibit FCV while maintaining low cytotoxicity, indicating its potential as a natural, water-soluble candidate for the suppression of norovirus. Full article

The nourishment of the human population depends on a handful of staple crops, such as maize, rice, wheat, soybeans, potatoes, tomatoes, and cassava. However, all crop plants are affected by at least one virus causing diseases that reduce yield, and in some parts of the world, this leads to food insecurity. Conventional management practices need to be improved to incorporate recent scientific and technological developments such as antiviral gene silencing, the use of double-stranded RNA (dsRNA) to activate an antiviral response, and nanobiotechnology. dsRNA with antiviral activity disrupt viral replication, limit infection, and its use represents a promising option for virus management. However, currently, the biggest limitation for viral diseases management is that dsRNA is unstable in the environment. This review is focused on the potential of nanoparticles and nanocarriers to deliver dsRNA, enhance stability, and activate antiviral gene silencing. Effective carriers include metal-based nanoparticles, including silver, zinc oxide, and copper oxide. The stability of dsRNA and the efficiency of gene-silencing activation are enhanced by nanocarriers, including layered double hydroxides, chitosan, and carbon nanotubes, which protect and transport dsRNA to plant cells. The integration of nanocarriers and gene silencing represents a sustainable, precise, and scalable option for the management of viral diseases in crops. It is essential to continue interdisciplinary research to optimize delivery systems and ensure biosafety in large-scale agricultural applications. Full article

The transmission of viruses and bacteria via surfaces remains a persistent challenge for healthcare systems, leading to high public health costs and significant environmental impact due to the widespread use and disposal of single-use products. This study aims to evaluate the feasibility of using surface-covering films, based on biopolymers and inorganic nanoparticles, with strong antiviral and antibacterial properties, as a strategy to prevent infection transmission while offering a sustainable alternative to disposable materials. To this end, we developed a sprayable chitosan-based solution embedded with copper oxide nanoparticles (CH.CA@Cu). The solution demonstrated antibacterial activity against both Gram-positive and Gram-negative bacteria as well as virucidal activity, predominantly within one minute of exposure, against a wide range of viruses. After spraying various materials, the resulting film surfaces exhibited excellent adherence and uniform coverage, maintaining their integrity after contact. A field trial conducted in high-traffic environments confirmed the coating’s effectiveness. This long-lasting antiviral action supports their implementation, since the coated surface can continuously deactivate viruses regardless of infective doses of exposure, thereby reducing viral transmission. These findings will expand biopolymers’ current applicability while guiding us toward the adoption of green and eco-friendly technologies, thus reducing waste production. Full article

The emergence of SARS-CoV-2 in 2019 posed significant global public health challenges. One of the most promising targets for novel antiviral drug development is the SARS-CoV-2 main protease (3CL^pro). In this study, fragment molecular orbital (FMO) calculations were conducted to provide guidance for the structural modification of natural flavonoids, identifying the pyrogallol moiety as a key candidate. Natural flavonoids were chemically modified to generate 33 semi-synthetic derivatives through the introduction of various functional groups. Our findings revealed that the incorporation of a galloyl moiety significantly enhances anti-proteolytic activity against SARS-CoV-2 3CL^pro, achieving up to a 23-fold increase compared to the activity of the parent compounds. Notably, 7-O-galloyl-DMC (40) exhibited the highest anti-proteolytic activity in an enzymatic assay. Additionally, molecular dynamics simulations provided atomic-level insights into the interactions between the galloyl moiety and 3CL^pro. All galloylated flavonoid derivatives positioned their galloyl groups within the S1′ sub-pocket, facilitating hydrogen bonding and π-interactions, particularly with Thr26 and Leu27. These findings underscore the potential of the galloyl moiety as a crucial structural element for enhancing the binding affinity of flavonoids with inhibitory activity against SARS-CoV-2 3CL^pro. Full article

Introduction: Fusobacterium nucleatum, a common oral microbe associated with periodontal disease, has emerged as a significant prognostic indicator in colorectal cancer (CRC). This organism is notably enriched in CRC tissues and is associated with reduced survival times and relapse. Fusobacterium is implicated in encouraging the development of chemoresistance through diverse tumor-promoting pathways that are increasingly being elucidated across molecular domains. Methods: This work uses a combined analysis of public data examining the role of F. nucleatum in CRC by investigating multiple transcriptomic datasets derived from co-culture infections in vitro. Results: In tandem with previously identified mechanisms known to be influenced by F. nucleatum, this analysis revealed that the bacterium activates multiple chemoresistance-associated pathways, including those driving inflammation, immune evasion, DNA damage, and metastasis. Notably, this study uncovered a novel induction of type I and type II interferon signaling, suggesting activation of a pseudo-antiviral state. Furthermore, pathway analysis (IPA) predicted altered regulation of several therapeutic agents, suggesting that F. nucleatum may compromise drug efficacy through transcriptional reprogramming. Conclusions: These findings reinforce the role of F. nucleatum in modulating host cellular pathways and support the hypothesis that bacterial association potentiates chemoresistance. Full article

This work thoroughly investigated the compound 4-(2,5-Dimethoxyphenyl)-3,4-dihydrobenzo[g]chromene-2,5,10-trione (DMDCT) using molecular docking, quantum chemical analysis, and vibrational spectroscopy methodology. The medicinal chemistry group has been particularly interested in chromene and benzochromene derivatives due to their wide range of pharmacological actions, including anticancer, antibacterial, anti-inflammatory, antioxidant, antiviral, and neuroprotective capabilities. In this connection, DMDCT has been explored to evaluate its biological, electrical, and structural properties. DFT using the B3LYP functional and 6–31G basis was established to conduct theoretical computations with the Gaussian 09 program. The findings from these computations provide insight into the following topics: NBO interactions, optimal molecular geometry, Mulliken charge distribution, frontier molecular orbitals, and MEP. Second-order perturbation theory has been used to assess stabilization energies arising from donor–acceptor interactions. Furthermore, general features such as chemical hardness, softness, and electronegativity were studied. The results suggest that DMDCT has stable electronic configurations and biologically relevant active sites. This integrated experimental and theoretical study supports the potential of DMDCT as a practical scaffold for future therapeutic applications and contributes valuable information regarding its vibrational and electronic behavior. Full article

Background: Encapsulating essential oils in polymer-based nanocarriers can improve their stability, solubility, and bioavailability, while maintaining the biological activity of the oil’s active ingredients. In this contribution, we investigated the antiviral activity of Oregano Essential Oil (OEO) in its pure form and encapsulated into nanosized polymeric micelles, based on a poly(ethylene oxide)-block-poly(ε-caprolactone) diblock copolymer. Methods: The effect of encapsulation was evaluated using three structurally different viruses: herpes simplex virus type 1 (HSV-1) (DNA—enveloped virus), human coronavirus (HCoV OC-43) (RNA—enveloped virus), and feline calicivirus (FCV) (RNA—naked virus). The effect on the viral replicative cycle was determined using the cytopathic effect inhibition (CPE) test. Inhibition of the viral adsorption step, virucidal activity, and protective effect on healthy cells were assessed using the final dilution method and were determined as Δlg compared to the untreated viral control. Results: In both studied forms (pure and nanoformulated), OEO had no significant effect on viral replication. In the remaining antiviral experiments, the oil embedded into nanocarriers showed a slightly stronger effect than the pure oil. When the oil was directly applied to extracellular virions, viral titers were significantly reduced for all three viruses, with the effect being strongest for HSV-1 and FCV (Δlg = 3.5). A distinct effect was also observed on the viral adsorption stage, with the effect being most significant for HSV-1 (Δlg = 3.0). Conclusions: Pretreatment of healthy cells with the nanoformulated OEO significantly protected them from viral infection, with the greatest reduction in viral titer for HCoV OC-43. Full article

Poly-γ-glutamic acid (γ-PGA), also known as polyglutamate, is a naturally derived polymer produced by Bacillus species that has demonstrated antiviral properties. Growing evidence from preclinical and clinical studies supports its therapeutic potential against various viral infections, highlighting both effective antiviral activity and a favorable safety profile. This review emphasizes current findings on the antiviral mechanisms of γ-PGA, including its ability to interfere with viral entry and to activate serial immune signaling pathways, with additional insights from structural biology. Collectively, γ-PGA represents a promising biomaterial for the development of future broad-spectrum antiviral strategies and applications. Full article

Cucumber green mottle mosaic virus (CGMMV) represents a serious threat in the production of watermelon. Small RNAs facilitate a mechanism known as RNA interference (RNAi), which regulates gene expression. RNAi technology employs foreign double-stranded RNAs (dsRNAs) to target and reduce the expression levels of specific genes in plants by interfering with their mRNAs. In this study, watermelon plants were treated with dsRNAs of CGMMV MET, IR, and HEL fragments that had been generated in E. coli HT115. We investigated variations in several factors, including viral accumulation, virus-derived small interfering RNAs (vsiRNAs), and symptom severity. MET-dsRNA, IR-dsRNA and HEL-dsRNA dramatically decreased the symptoms of CGMMV in plants in the growth chamber test. Plants treated with viral-derived dsRNA showed a considerable decrease in both virus titers and vsiRNA levels. We also explored the mobility of spray-on dsRNA-derived long dsRNA and discovered that it could be identified in both inoculated leaves and the systemic leaves. IR-dsRNA outperformed MET-dsRNA and HEL-dsRNA in dsRNA therapy. Illumina sequencing of small RNAs from watermelon plants treated with IR-dsRNA and those that were not treated showed that the decreased accumulation of vsiRNAs was consistent with interference with CGMMV infection in systemic leaves. dsRNA-treated plants showed a higher level of 24-nt viral siRNA and lower level of 22-nt viral siRNA accumulation, while 22-nt viral siRNA predominated in untreated plants, indicating that dsRNA treatment improved DCL3 activity. In conclusion, our research provides deeper insights into the mechanism of antiviral RNA interference and confirms the effectiveness of applying dsRNA locally to enhance plant antiviral activity. Full article