In silico exploration of 4(α-l-rhamnosyloxy)-benzyl isothiocyanate: A promising phytochemical-based drug discovery approach for combating multi-drug resistant Staphylococcus aureus.

Multidrug-resistant (MDR) Staphylococcus aureus infections significantly threaten global health. With rising resistance to current antibiotics and limited solutions, the urgent discovery of new, effective, and affordable antibacterials with low toxicity is imperative to combat diverse MDR S. aureus strains. Hence, in this study, we introduce an in silico phytochemical-based approach for discovering novel antibacterial agents, underscoring the potential of computational approaches in therapeutic discovery. Glucomoringin Isothiocyanate (GMG-ITC) from Moringa oleifera Lam. is one of the phytochemical compounds with several biological activities, including antimicrobial, anti-inflammatory, and antioxidant activities, and is also effective against S. aureus. This study focuses on screening GMG-ITC as a potential drug candidate to combat MDR S. aureus infections through a molecular docking approach. Moreover, interaction amino acid analysis, in silico pharmacokinetics, compound target prediction, pathway enrichment analysis and molecular dynamics (MD) simulations were conducted for further investigation. Molecular docking and interaction analysis showed strong binding affinity towards S. aureus lipase, dihydrofolate reductase, and other MDR S. aureus proteins, including penicillin-binding protein 2a, MepR, D-Ala:D-Ala ligase, and RPP TetM, through hydrophilic and hydrophobic interactions. GMG-ITC also showed a strong binding affinity to cyclooxygenase-2 and FAD-dependent NAD(P)H oxidase, suggesting that it is a potential anti-inflammatory and antioxidant candidate that may eliminate inflammation and oxidative stress associated with S. aureus infections. MD simulations validated the stability of the GMG-ITC molecular interactions determined by molecular docking. In silico pharmacokinetic analysis highlights its potency as a drug candidate, showing strong absorption, distribution, and excretion properties in combination with low toxicity. It acts as an active protease and enzyme inhibitor with moderate activity against GPCR ligands, ion channels, nuclear receptor ligands, and kinases. Enrichment analysis further elucidated its involvement in important biological, molecular, and cellular functions with potential therapeutic applications in diseases like cancer, hepatitis B, and influenza. Results suggest that GMG-ITC is an effective antibacterial agent that could treat MDR S. aureus-associated infections.

Microbial diversity characterizations, associated pathogenesis and antimicrobial resistance profiling of Najafgarh drain.

The Najafgarh drain plays a significant role in the pollution of the Yamuna River, accounting for 40% of the total pollution. Therefore, it is crucial to investigate and analyze the microbial diversity, metabolic functional capacity, and antibiotic resistance genes (ARGs) present in the Najafgarh drain. Additionally, studying the water quality and its relationship with the proliferation of microorganisms in the drain is of utmost importance. Results obtained confirmed the deteriorated water quality as physico-chemical parameters such as biochemical oxygen demand (BOD), chemical oxygen demand (COD), dissolved oxygen (DO), and total suspended solids (TSS) in the range of 125-140, 400-460, 0-0.2, 25-140.4 mg/l respectively violated the standard permissible national and global standards. In addition, the next generation sequencing (NGS) analysis confirm the presence of genus such as Thauera, Arcobacter, Pseudomonas, Geobacter, Dechloromonas, Tolumonas, Sulfurospirullum, Desulfovibrio, Aeromonas, Bacteroides, Prevotella, Cloacibacterium, Bifidobacterium, Clostridium etc. along with 864 ARGs in the wastewater obtained from the Najafgarh drain. Findings confirm that the pathogenic species reported from this dataset possess severe detrimental impact on faunal and human health. Further, Pearson's r correlation analysis indicated that environmental variables, mainly total dissolved solids (TDS) and chemical oxygen demand (COD), play a pivotal role in driving microbial community structure of this heavily polluted drain. Thus, the poor water quality, presence of a microbial nexus, pathogenic markers, and ARGs throughout this drain confirmed that it would be one potential contributor to the dissemination of disease-causing agents (pathogens) to the household and drinking water supplies in the near future.