Introduction: Finding potential antiviral inhibitors has advanced significantly through computer-aided drug discovery. Methods: The Random Forest regression (RFR), PLS regression, NNKernel regression, and pcRegression models were compared and assessed using R². In the following step, molecular docking was conducted to assess binding affinities and protein-ligand interactions. The ligand with the highest ICM score was subjected to molecular dynamics simulations to analyze binding and mechanism. In the final step, network pharmacology was adopted to study the mechanism of action. Results: The R² value for RFR is 0.93, indicating that the model performed exceptionally well in terms of prediction, with highly correlated experimental and predicted values. The ML model showed that only 152 out of the 186 compounds have pIC50 values greater than 6. Ligands with pIC50 values greater than 6 were selected for molecular docking with the NS2B/NS3 protease. Molecular docking studies revealed that 28 of the 152 compounds have ICM scores below 0, and five compounds were selected at the top of the list based on their binding interactions and ICM scores. The compound that was ranked highest, PubChem IDs 44626355, 166633044, 166633428, 20873605, and 166626117, had ICM scores of -21.657148, -19.151558, -16.963572, -16.836168, and -15.635322 kcal/mol. Discussion: PubChem CID: 44626355 compound’s binding stability is attributed to strong hydrogen bonding, van der Waals, and hydrophobic interactions. Molecular dynamics simulations, PCA, and FEL were conducted. Through network pharmacology, the therapeutic mechanism emerges that acts across several interconnected pathways involved in dengue pathology. Conclusion: Our study offers a promising framework for identifying potent inhibitors of the dengue virus.
Abstract: Corneal infection that can cause blindness, fungal keratitis has shown an increasing prevalence worldwide, especially in tropical and subtropical areas, where it significantly increases the risk of unilateral corneal blindness. The epidemiology, molecular etiology, diagnosis, antifungal resistance, and changing treatment of fungal keratitis are all reviewed in this article. Geographic diversity is evident in epidemiological patterns, with filamentous fungi such as Aspergillus and Fusarium predominating in warm climes, and an increasing number of reports of Candida species in temperate and healthcare-associated settings. Disease incidence and outcomes have been further affected by post-COVID-19 changes in ophthalmic treatment, extensive corticosteroid exposure, delayed presentations, and environmental factors, including climate fluctuations and increased airborne spore loads. Rapid stromal invasion, enzyme-mediated tissue damage, biofilm development, and host immune dysregulation are key factors determining severity, according to molecular findings. For improved detection, including in culture-negative and polymicrobial cases, diagnostic advancements focus on combining traditional microscopy and culture with in vivo confocal microscopy, MALDI-TOF MS, targeted PCR, and metagenomic next-generation sequencing. Time to treatment is being reduced by rapid point-of-care techniques like tear β-D-glucan tests, LAMP, CRISPR/Cas platforms, and AI-based image analysis. The necessity for systematic susceptibility testing and antifungal management is supported by rising antifungal resistance, particularly rising MIC trends in Fusarium and Aspergillus species, which exhibit variable susceptibility to azoles and amphotericin B, highlighting the need for species-specific antifungal susceptibility testing. The evolving epidemiology, molecular etiology, and new developments in fungal keratitis diagnosis are covered in this article. Additionally, it emphasizes new therapeutic approaches, including advanced drug delivery systems, advances in antifungal resistance management, and potential avenues for improved management. The article presents a narrative review focusing on recent developments in the epidemiology, molecular mechanisms, diagnosis, antifungal resistance, and treatment options for fungal keratitis.
Introduction: This study aimed to characterize the chemical and biological properties of Ocimum lamiifolium Hochst. ex Benth. (family: Lamiaceae) leaf extracts and explore their potential applications. Methods: Plant leaves were extracted with ethanol via maceration and hydrodistillation, yielding 5.95% (w/w) and 2.25% (v/w) extracts, respectively. The chemical compositions were identified using gas chromatography-mass spectrometry (GC-MS) and Fourier-transform infrared spectroscopy (FTIR). Using 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assays, both the ethanolic extract and the essential oil were evaluated for antioxidant activity. Results: Thirty compounds, primarily monoterpenoids, accounted for 81.13% of the total components of the O. lamiifolium essential oil. 55 compounds were identified in the crude ethanolic extract, accounting for 99% of the total. Hydrocarbon terpenes were particularly abundant in the crude ethanolic extract. The plant extracts showed promising antioxidant activity, with the EO and EE extracts having IC50 values of 1.56 and 2.52 μg/mL, respectively, compared with the reference stand-ard ascorbic acid, which had an IC50 of 3.90 μg/mL. Discussion: Compared to the EO extract, the EE extract exhibited larger inhibition zones. The antimicrobial results suggest that the EE extract contains more active components, as proven by the GC-MS results. Molecular docking analysis of the three identified components revealed that δ-cadinene exhibited the highest binding affinity and formed hydrophobic interactions with 8 amino acids. This implies that these compounds may function as DNA gyrase inhibitors. Conclusion: O. lamiifolium extracts have potential applications as antibacterial and antioxidant agents.
Introduction: Leishmania sp. can cause visceral, mucosal, cutaneous, and subcutaneous forms. Leishmania major is responsible for the cutaneous manifestation of the disease. Due to the limited treatment options and growing resistance in the disease, an in-silico study was conducted to find new therapeutic targets in L. major. Methods: The choke point reactions present in the LeishCyc database were utilized to identify the enzymes responsible for catalyzing these reactions, to discover novel therapeutic targets. The sub-tractive genome approach was used to compare these enzymes with the human proteome to avoid off-target effects. The subcellular location of these enzymes was additionally predicted using DeepLock 2.0. Afterwards, protein-protein interactions were analyzed with STRINGv12.0, identi-fying high-confidence enzymes with highly ranked clusters. Their pathways and significance in parasite survival were determined via the Kyoto Encyclopedia of Genes and Genomes and relevant literature. Afterwards, the uniqueness of pharmacological targets and the potential for broad-spec-trum activity of relevant enzymes were assessed using the DrugBank database and BLASTp anal-ysis. Additionally, 3D structures were modeled and validated using SWISS MODEL and SAVESv6.0. Results: The study proposed that Putative lanosterol 14-alpha demethylase, DPMS, and ADS1 have the potential to be effective therapeutic targets due to their innovative nature. An extensive investigation using BLASTp revealed that these selected pharmacological targets exhibit more than 90% similarity with other Leishmania species, suggesting their potential for therapeutic targeting throughout the Leishmania genus. Conclusion: The prospective pharmacological targets revealed in this work, specifically the puta-tive lanosterol 14-alpha demethylase, DPMS, and ADS1, show promise for future investigation as potential therapeutic targets. Nevertheless, further in-vitro and in-vivo investigations are required to fully examine their complete therapeutic capabilities.
INTRODUCTION:Long COVID syndrome (LCS) is characterized by persistent neurological, respiratory, and systemic symptoms following SARS-CoV-2 infection, with limited effective treatments available. Viusid is an oral antioxidant and immunomodulatory formulation that may improve chronic inflammatory symptoms. This study evaluated the efficacy of Viusid in patients with LCS. METHODS:This randomized double-blind placebo-controlled clinical trial evaluated the efficacy and safety of Viusid in adults with long COVID syndrome. The primary endpoint was the change in brain fog severity at Day 210. Secondary endpoints included changes in neurological, respiratory, musculoskeletal, digestive, and general symptoms measured using a 23-symptom clinical questionnaire. RESULTS:All participants completed the study. Viusid significantly improved the primary endpoint, brain fog, compared with placebo (MD -1.23; 95% CI -2.41 to -0.005; p < 0.001). Significant improvements favoring Viusid were also observed in anxious-depressive mood (p < 0.001), sleep dis-orders (p = 0.003), fatigue (p = 0.023), dyspnea (p = 0.018), chest pain (p = 0.002), cough (p = 0.004), abdominal pain (p = 0.009), and myalgia (p = 0.025). These effects remained consistent after adjusted analyses. DISCUSSION:The intervention showed potential improvement in long COVID symptoms; however, the small sample size and observational design limit conclusions, warranting further randomized con-trolled studies. CONCLUSIONS:Viusid significantly improved multiple long COVID symptoms, particularly neurological and respiratory manifestations. These findings support its potential as a therapeutic option for long COVID and justify further confirmatory studies.
