Search Results (2,444)

Acorus calamus, a traditional Tibetan medicine with potential antiviral activity but undefined mechanisms, was studied for its anti-respiratory syncytial virus (RSV) mechanisms using network pharmacology and molecular docking, given RSV’s substantial disease burden and lack of specific therapies. The primary active compounds were identified and analyzed through a literature search, the PubChem database, and the SwissADME. Relevant targets were sifted through the SwissTargetPrediction platform, OMIM, and GeneCards databases. Common targets underwent enrichment analysis using Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG). Molecular docking and GEO datasets were used for further analysis. Among the screened data, 268 targets were associated with Acorus calamus compounds and 1633 with RSV. KEGG analysis of the shared targets revealed potential therapeutic roles via the PI3K–Akt and JAK–STAT signaling pathways. Molecular docking results demonstrated that CCND1, EGFR, and SRC exhibited relatively lower binding energies with compounds in comparison to other proteins, suggesting better interactions, and GEO-derived RSV datasets further validated CCND1’s significance. This study demonstrates Acorus calamus’s anti-RSV activity and its potential mechanism, providing a theoretical foundation for the effective active ingredients of Acorus calamus targeting CCND1 as a strategy to combat RSV infection. Full article

Marine natural products have gained increasing interest in drug research and development because of their unique structures, diverse biological activities, and novel mechanisms of action. Using the antiviral alkaloid aldisine as the lead compound and utilizing the hydrogen bond effects common in drug design, novel derivatives containing an acylhydrazone moiety were designed and synthesized. The structures of these derivatives were systematically analyzed using variable-temperature ¹H-NMR. Antiviral activity tests showed that most derivatives were active against tobacco mosaic virus (TMV), with some compounds outperforming the commercial antiviral drug ribavirin. Notably, 3-methylphenyl- and 3-pyridyl-substituted acylhydrazones 5-6 and 5-12 displayed activity comparable to ningnanmycin, one of the most effective commercial antiviral agents. Molecular docking results indicated that incorporating the acylhydrazone moiety enhances hydrogen bonding between the molecules and target proteins. Additionally, we evaluated the fungicidal and larvicidal activities of these derivatives. Most exhibited significant larvicidal effects against Mythimna separata and Plutella xylostella, along with broad-spectrum fungicidal activity. Four related compounds (5-11, 5-12, 5-13, and 5-17) exhibited high fungicidal activities, and another four compounds (2-4, 5-6, 5-13, and 5-17) exhibited high larvicidal activities. Full article

The use of antibiotics as growth promoters (AGPs) has been a common practice in animal production; however, concerns over microbial resistance have led organizations, such as the FAO, EU, and EFSA, to restrict or ban their use. This has prompted a growing interest in natural alternatives, particularly medicinal herbs, for enhancing animal performance and health. Among these, Scutellaria baicalensis (Chinese Skullcap) and Lonicera japonica (Japanese Honeysuckle) have gained attention for their high medicinal value in monogastric animal diets. These plants contain bioactive compounds, such as flavones (baicalin, baicalein, oroxylin A), iridoids (loganin), and saponins (including loniceroside hederagenin), which exhibit a range of biological activities, including antioxidative, anti-inflammatory, antibacterial, antiviral, and anti-stress effects. Notably, these herbal extracts are natural, safe, and unlikely to induce microbial resistance. Recent studies suggest that supplementation with S. baicalensis and L. japonica can improve livestock production performance by mitigating oxidative stress. This review aims to highlight the potential application of these plant-based additives in reducing oxidative damage and enhancing productivity in animal agriculture. Full article

Influenza A virus pandemics pose a persistent global health threat, and emerging antiviral resistance underscores the critical importance of developing novel broad-spectrum therapeutic agents. Building on licorice’s (Glycyrrhiza spp.) historical use in traditional Chinese medicine for respiratory infections—as documented in the Chinese Guidelines for Diagnosis and Treatment of Influenza—and its demonstrated anti-SARS-CoV-2 activity, we identified licoflavone B as a potent anti-influenza agent, bridging ethnopharmacological knowledge with mechanistic validation. In this study, we identified licoflavone B, a natural flavonoid derived from licorice (Glycyrrhiza spp.), as a potent inhibitor of diverse influenza viruses, including multiple influenza A subtypes and type B virus. Mechanistic studies revealed that licoflavone B selectively targets the viral RNA-dependent RNA polymerase (RdRp), effectively suppressing viral replication. The compound exhibits a favorable selectivity index (SI = 14.9–29.9), indicating a promising therapeutic window. Molecular docking simulations identified potential binding interactions between licoflavone B and regions of the RdRp complex, which were further validated by dose-dependent inhibition of viral nucleoprotein (NP) and polymerase subunit PB2 expression in Western blot and immunofluorescence assays. In addition, licoflavone B maintained broad-spectrum antiviral activity against multiple influenza strains, including H1N1 (A/Puerto Rico/8/34), H3N2 (A/Darwin/9/2021), and a clinical influenza B isolate (B/Beijing/ZYY-B18/2018). These findings position licoflavone B as a promising lead compound for developing next-generation, broad-spectrum antiviral therapies against influenza and potentially other viruses. Full article

Deoxyshikonin (DS) is a derivative of shikonin, the main compound present in Lithospermi radi, the root of Lithospermum erythrorhizon Siebold and Zucc. In this study, we investigated the antiviral effects of DS using Influenza A/PR8/34, which expresses green fluorescent protein (GFP) as well as wild-type PR8/34 H1N1 Influenza A virus (IAV). Fluorescence microscopy and flow cytometry results showed that DS from 1.25 to 5 µM significantly and dose-dependently inhibited PR8-GFP IAV infection. A plaque assay confirmed the inhibitory effect of DS against H1N1 IAV infection. Consistently, immunofluorescence results showed that DS suppresses IAV protein expression. Time-of-drug-addition and hemagglutination inhibition assays revealed that DS exhibits anti-influenza virus efficacy by blocking the viral attachment and penetration into the cells and has a direct virus-eradication effect in the early stages of infection. However, DS did not repress neuraminidase activity. Our findings suggest that DS could be used not only to protect against the early stages of IAV infection, but also to treat influenza virus infections in combination with NA inhibitors. Full article

Chronic, low-grade inflammation is a key contributor to the development of numerous non-communicable diseases (NCDs), including cardiovascular, metabolic, and neurodegenerative disorders. Conventional anti-inflammatory drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, often present safety concerns with prolonged use, highlighting the need for safer, multi-targeted therapeutic options. Iridoids, a class of monoterpenoid compounds abundant in several medicinal plants, have emerged as promising bioactive agents with diverse pharmacological properties. They exert anti-inflammatory and metabolic regulatory effects by modulating key signaling pathways, including nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), Janus kinase/signal transducer and activator of transcription (JAK/STAT), adenosine monophosphate-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor (PPAR) pathways. This review provides a comprehensive summary of the major iridoid metabolites derived from ten Bulgarian medicinal plant species, along with mechanistic insights from in vitro and in vivo studies. Documented biological activities include anti-inflammatory, antioxidant, immunomodulatory, antifibrotic, organoprotective, antibacterial, antiviral, analgesic, and metabolic effects. By exploring their phytochemical profiles and pharmacodynamics, we underscore the therapeutic potential of iridoid-rich Bulgarian flora in managing inflammation-related and metabolic diseases. These findings support the relevance of iridoids as complementary or alternative agents to conventional therapies and highlight the need for further translational and clinical research. Full article

Zika virus (ZIKV) remains a pressing global health concern due to its association with congenital Zika syndrome and the current lack of approved antiviral therapies. In this study, we evaluated the antiviral activity of three novel thiazolidinedione derivatives, GQ-402, GQ-396, and ZKC-10, against ZIKV in vitro and investigated their potential molecular targets through in silico analysis. GQ-402 exhibited the highest antiviral potency, with an IC₅₀ of 15.7 µM, while ZKC-10 achieved the most substantial reduction in viral RNA levels, as determined by RT-qPCR. Molecular docking studies identified GQ-396 as the top-ranked inhibitor of the NS2B-NS3 protease and NS5 RNA-dependent RNA polymerase, suggesting distinct mechanisms of action among the compounds. These findings highlight the therapeutic potential of thiazolidinedione derivatives and underscore the need for further investigation to develop effective treatments for ZIKV infection. Full article

Objective: This study aims to investigate the pharmacodynamic effects and underlying mechanisms of the Chinese herbal formula RuHaoDaShi (RHDS) granules against the influenza virus in experimental models. Methods: This study aims to employ network pharmacology to identify the active components of RHDS and its potential targets and mechanisms of action against H1N1. The molecular docking approach validated the interactions between the core targets and the RHDS compounds. In vitro, the antiviral activity of RHDS was assessed by therapeutic, prophylactic, and premixed administration to H1N1-infected A549 cells. An in vivo experiment was conducted using a mouse H1N1 pneumonia model. The model was treated with a dose of 1.04, 2.08, and 4.16 g/kg of RHDS, administered via gavage daily. The study’s objective was to evaluate the antiviral activity and mechanism of action of RHDS in mice. Mice were evaluated on day 6 by assessing survival, viral load (RT-qPCR), lung pathology (HE staining), inflammatory cytokines (ELISA, immunohistochemistry), and ferroptosis markers (WB, qPCR). Results: Network pharmacology identified 77 biologically active RHDS compounds (e.g., quercetin and kaempferol) and 32 core targets common to RHDS, H1N1, and ferroptosis. Molecular docking was used to verify a high affinity for binding between the core targets HIF-1α, MAPK3, and key RHDS compounds. In vitro studies demonstrated that RHDS exhibited protective properties against H1N1-infected cells, with the therapeutic delivery method proving the most efficacious. In vivo studies have shown that RHDS reduces mortality, lung index, and viral load in mice while attenuating histopathological damage. The study demonstrated a reduction in the release of inflammatory cytokines, including IL-6, IFN-γ, and IL-17A, and decreased expression levels of MPO and F4/80 proteins in lung tissue. Mechanistically, the administration of RHDS resulted in the up-regulation of the expression levels of GPX4, SLC7A11, and Nrf2 proteins while concomitantly inhibiting the expression of HIF-1α, COX2, and ACSL4. These findings confirm the modulatory effect of RHDS on the GPX4/SLC7A11/Nrf2 pathway. Conclusions: RHDS demonstrated a protective effect against H1N1-induced cytopathy in vitro and was effective in attenuating H1N1-induced pneumonia in murine models. The study suggests that RHDS has antiviral potential to treat H1N1 viral pneumonia by modulating inflammatory cytokines and the GPX4/SLC7A11/Nrf2 pathway. Full article

Background: Heterocyclic compounds represent a key class of compounds in medicinal chemistry. Both benzimidazoles and pyrimidines are essential heterocycles in medicinal chemistry, with various therapeutic properties. Recent literature presents a series of hybrid heterocyclic compounds, as their medicinal properties are generally improved compared to those of single heterocyclic rings. Methods: A literature search was conducted across relevant scientific literature from peer-reviewed sources, using keywords, including “benzimidazole”, “pyrimidine”, “Biginelli”, “benzimidazole-pyrimidine hybrids”, “anticancer”, “antiviral”, “antimicrobial”, and “anti-inflammatory”. Results: In this review, benzimidazole–pyrimidine hybrids are reported as anticancer, antimicrobial, antiviral, anti-inflammatory, analgesic, antiulcer, antidepressant, anti-Alzheimer’s, or antioxidant agents, with activities even better than those of existing drugs. The IC₅₀ values for these anticancer hybrids are in the nanomolar range, which signifies potent anticancer agents. It can be mentioned here that the anticancer hybrid Abemaciclib, as a CDK4/6 inhibitor for the treatment of certain types of breast cancer, was approved in 2017. The antimicrobial activity of these hybrids proved especially potent against a broad variety of infections, with MIC values in the range of µM or even nM. Moreover, these hybrids exhibited good antiviral properties against SARS-CoV-2, HIV-1, and the hepatitis C virus. The hybrids also functioned as JAK3 inhibitors, COX-1 inhibitors, and MAO-A inhibitors. Conclusions: This review presents synthesis methods of benzimidazole–pyrimidine hybrids, their medicinal properties, and SAR studies reported in the last 20 years. For almost every therapeutic activity, SAR studies have revealed the essential presence of a substituent on the aromatic rings or between the two benzimidazole and pyrimidine nuclei. Full article

Natural products possess a wide range of biological and biochemical potentials, with plant-derived compounds being significant sources for discovering new drugs. In this study, extracts of Vitex negundo and Macaranga tanarius prepared with different solvents were tested for their antiviral activity against the original SARS-CoV-2 Wuhan strain and its variants using plaque assay, quantitative real time RT-PCR, and immunofluorescence assay (IFA). Our results showed that at their maximum non-toxic concentrations, Vitex-Dichloromethane (DCM) and Macaranga extracts significantly inhibited SARS-CoV-2 Wuhan strain growth in Vero E6 cells, showing a 5-log reduction in plaque assay and confirmed by IFA. Meanwhile, Vitex-Hexane showed moderate activity with a 2-log decrease. The inhibition was shown in a dose-dependent manner. The antiviral efficacy of these extracts was further demonstrated against various SARS-CoV-2 variants including Alpha, Beta, Delta, and Omicron. Both Vitex-DCM and Macaranga showed strong virucidal activity. In addition, Vitex-DCM and Macaranga inhibited the transcriptional activity of purified SARS-CoV-2 RdRp, indicating that RdRp inhibition may contribute to viral suppression as shown at the post-infection stage. Furthermore, combining Vitex-DCM or Macaranga with remdesivir showed a synergistic effect against SARS-CoV-2. These results suggest that Vitex negundo and Macaranga tanarius extracts are promising candidates for anti-SARS-CoV-2 treatments. Their synergy with remdesivir also underscores the potential of drug combinations in fighting SARS-CoV-2 and preventing the emergence of mutant variants. Full article

Despite the widespread use of vaccines against SARS-CoV-2, COVID-19 continues to pose global health challenges, requiring efficient drug screening and repurposing strategies. This study presents a novel hybrid framework that integrates deep learning (DL) with molecular docking to accelerate the identification of potential therapeutics. The framework comprises three crucial steps: (1) a previously developed DL model is employed to rapidly screen candidate compounds, selecting those with predicted interaction scores above a cut-off value of 0.8; (2) AutoDock Vina version 1.5.6 and LeDock version 1.0 are used to evaluate binding affinities, with a threshold of <−7.0 kcal·mol⁻¹; and (3) predicted drug–protein binding sites are evaluated to determine their overlap with known active residues of the target protein. We first validated the framework using four experimentally confirmed COVID-19 drug–target pairs and then applied it to identify potential inhibitors of the SARS-CoV-2 main protease (M^Pro). Among 29 drug candidates selected based on antiviral, anti-inflammatory, or anti-cancer properties, only Enasidenib met all three selection criteria, showing promise as an M^Pro inhibitor. However, further experimental and clinical studies are required to confirm its efficacy against SARS-CoV-2. This work provides an interpretable strategy for virtual screening and drug repurposing, which can be readily adapted to other DL models and docking tools. Full article

Feline infectious peritonitis virus (FIPV), caused by a mutated form of feline coronavirus, poses a significant threat to feline health worldwide, with limited therapeutic options available. This study investigated the antiviral potential of α-mangostin (α-MG) and its enriched extracts (AMEs), obtained via microwave-assisted extraction, against FIPV. We evaluated their cytotoxicity, direct virucidal activity, and antiviral activity in CRFK cells. Both α-MG and AMEs demonstrated significant antiviral activity, with EC₅₀ values from 2.71 to 2.88 μg/mL and favorable selectivity indices (3.25–3.66). Notably, AMEs exhibited direct virucidal effects, effectively reducing viral titers. Furthermore, treatment with these compounds significantly reduced inflammatory cytokine expression (IFN-β, TNF-α, and IL-6 mRNA levels) and decreased viral loads in FIPV-infected cells. Drug combination studies using the ZIP model revealed enhanced cooperative effects when AMEs and α-MG were combined with GC-376 or GS-441524, with GC-376 combinations showing particularly strong synergistic potential. These findings suggest that α-MG and AMEs are promising candidates for FIPV treatment, either as monotherapy or in combination therapy. This study provides insights into developing novel therapeutic strategies to combat FIPV infections and offers a foundation for future veterinary antiviral drug development. Full article

Black tea is one of the most widely consumed beverages in the world, second only to water. Its properties are primarily due to the presence of polyphenols, which are associated with various effects, including antioxidant, anticancer, antiviral, and anti-inflammatory activities. These compounds include, among others, theaflavins (TFs) and thearubigins (TRs). The available literature provides numerous reports confirming the positive properties of these compounds. However, it is important to highlight their potential protective effects against oxidative stress induced by heavy metals. This is an important topic, given the ongoing exposure to such pollutants—resulting mainly from industrial development, among other factors. This manuscript provides a summary of the current knowledge on the properties of TFs and TRs and their effect against oxidative stress caused by heavy metals in in vitro studies. The limited amount of research in this area shows that this is still a poorly researched topic. Comparing the results obtained for epigallocatechin gallate (EGCG) from green tea, which has a similar structure to TFs and TRs suggests that they may exhibit similar or even enhanced antioxidant properties. Considering that black tea is consumed much more frequently than green tea worldwide, it is understandable that the antioxidant potential of these two compounds on cells needs to be investigated. Full article

Lower respiratory infections predominantly affect children under five and the elderly, with influenza viruses and respiratory syncytial viruses (including SARS-CoV-2) being the most common pathogens. The COVID-19 pandemic has posed significant global public health challenges. While vaccination remains crucial, its efficacy is limited, highlighting the need for complementary approaches to mitigate immune hyperactivation in severe COVID-19 cases. Medicinal plants like Cannabis sativa show therapeutic potential, with over 85% of SARS-CoV-2-infected patients in China receiving traditional herbal treatments. This review explores the antiviral applications of cannabis and its bioactive compounds, particularly against SARS-CoV-2, while evaluating their pharmacological and food industry potential. Cannabis contains over 100 cannabinoids, terpenes, flavonoids, and fatty acids. Cannabinoids may block viral entry, modulate immune responses (e.g., suppressing pro-inflammatory cytokines via CB2/PPARγ activation), and alleviate COVID-19-related psychological stress. There are several challenges with pharmacological and food applications of cannabinoids, including clinical validation of cannabinoids for COVID-19 treatment and optimizing cannabinoid solubility/bioavailability for functional foods. However, rising demand for health-focused products presents market opportunities. Genetic engineering to enhance cannabinoid yields and integrated pharmacological studies are needed to unlock cannabis’s full potential in drug discovery and nutraceuticals. Cannabis-derived compounds hold promise for antiviral therapies and functional ingredients, though further research is essential to ensure safety and efficacy. Full article

In this study, astaxanthin, which has previously been shown to have antiviral effects, was examined for its dose-dependent potency to inhibit cellular SARS-CoV-2 infections. Naturally occurring astaxanthin is obtained and orally administered as ASX-oleoresin, a composition of different astaxanthin fatty acid esters. We therefore hypothesized that the compound’s beneficial effects are not only related to astaxanthin. Thus, a “green” algae extract (i.e., poor astaxanthin content < 0.2%; ASX^p) of the microalgae Haematococcus pluvialis, as well as an astaxanthin-rich algae extract (astaxanthin content = 20%; ASX^r), were tested in in vitro cellular viral infection assays. Thereby, it was found that both extracts reduced viral infections significantly. As a potential mode of inhibitory action, the binding of ASX-oleoresin to the viral spike protein was investigated by isothermal fluorescence titration, revealing binding affinities of Kd = 1.05 µM for ASX^r and Kd = 1.42 µM for ASX^p. Based on our data, we conclude that several ASX-oleoresin fractions from H. pluvialis exhibit antiviral activity, which extends beyond the known antioxidant activity of astaxanthin. From a molecular dynamic simulation of ASX-oleoresin, fatty acid domains could be considered as activity-chaperoning factors of ASX. Therefore, microalgae biomass should be considered in the future for further antiviral activities. Full article