This study explores the potential anti-H1N1 Influenza A activity of bioactive compounds extracted from Streptomyces ardesiacus, a marine-derived microorganism known for producing diverse secondary metabolites. Four major compounds—1-acetyl-β-carboline, 1H-indole-3-carbaldehyde, anthranilic acid, and indole-3-carboxylic acid—were isolated and characterized through NMR. Among these, the identified structure of 1-acetyl-β-carboline showed the highest IC₅₀ effect, with a dose of 9.71 μg/mL in anti-influenza assays. Using network pharmacology and molecular docking analyses, the interactions of these compounds with key proteins involved in H1N1 pathogenesis were examined. Protein–protein interaction (PPI) networks and Gene Ontology enrichment analysis revealed CDC25B, PARP1, and PTGS2 as key targets, associating these compounds with pathways related to catalytic activity, inflammation, and cell cycle regulation. The molecular docking results demonstrated that 1-acetyl-β-carboline exhibited binding affinities comparable to Tamiflu, the positive control drug, with LibDock scores of 81.89, 77.49, and 89.21 for CDC25B, PARP1, and PTGS2, respectively, compared to Tamiflu’s scores of 84.34, 86.13, and 91.29. These findings highlight the potential of the active compound 1-acetyl-β-carboline from S. ardesiacus as a novel anti-influenza agent, offering insights into their molecular mechanisms of action. The results support further in vitro and in vivo studies to validate the observed inhibitory mechanisms and therapeutic applications against H1N1 Influenza A.

Clusterin is one of the many known proteins implicated in cancer chemoresistance, which hinders the effectiveness of chemotherapy. This study aimed to design novel inhibitors targeting clusterin using fragment-based drug discovery (FBDD). This approach aims to develop new medicines by identifying small, simple molecules known as “fragments” that can bind to a specific target, such as a disease-causing protein. In this study, a primary ligand-binding site and an allosteric site on the clusterin molecule were identified through hotspot analysis. We screened commercially available fragment libraries for anti-cancer activity and applied the “rule of three” to ensure drug-like properties. The highest-affinity fragment underwent “fragment-growing” to develop potential drug candidates. After docking and toxicity screening, 194 candidate drugs were identified. Quantitative structure-activity relationship (QSAR) analysis revealed that the chemical size and complexity of the fragments significantly contributed to their binding affinity. Pharmacokinetic analyses of candidate drugs from FBDD followed by molecular dynamics simulation of the top 1 final candidate drug precursor demonstrated comparatively better affinity (average = −34.01 kcal/mol) than the reference compound (average = −6.15 kcal/mol) and significant ligand flexibility. This study offers a potential strategy to identify fragments or molecules that may serve as drugs against clusterin-related chemoresistance.

Dyspepsia or indigestion is known to be a symptom of several gastrointestinal issues including gastroesophageal reflux disease (GERD) and gastric cancer. With the ever-increasing popularity of traditional herbal medicines, the research selected rosemary, or Salvia rosmarinus, due to its historical ethnopharmacological applications and ease of cultivation. Potential targets of molecules from S. rosmarinus are explored for the molecular pathogenesis of functional dyspepsia. Through a network pharmacology approach, it has been shown that there is a significant interaction between the disease and the plant’s compounds. The pathways involving the target genes of S. rosmarinus that are related to functional dyspepsia were revealed to be implicated in the development of certain diseases like gastric cancer and fibrosis which are both precursors to dyspepsia. Moreover, through molecular docking, the results of the pathway analyses were computationally validated indicating that the compound luteolin has the most significant interaction against dyspepsia-related genes. It effectively promotes apoptosis in cancer pathways, reducing the chances of gastric cancer carcinogenesis. To further validate these findings, molecular dynamics simulation was performed to compare the stability and binding behavior of the top-performing compound against the reference compound. The results of this study could be a possible basis in developing pharmaceuticals against gastrointestinal diseases, specifically, dyspepsia.