CSC01 shows promise as a potential inhibitor of the oncogenic G13D mutant of KRAS: an in silico approach.

About 30% of malignant tumors include KRAS mutations, which are frequently required for the development and maintenance of malignancies. KRAS is now a top-priority cancer target as a result. After years of research, it is now understood that the oncogenic KRAS-G12C can be targeted. However, many other forms, such as the G13D mutant, are yet to be addressed. Here, we used a receptor-based pharmacophore modeling technique to generate potential inhibitors of the KRAS-G13D oncogenic mutant. Using a comprehensive virtual screening workflow model, top hits were selected, out of which CSC01 was identified as a promising inhibitor of the oncogenic KRAS mutant (G13D). The stability of CSC01 upon binding the switch II pocket was evaluated through an exhaustive molecular dynamics simulation study. The several post-simulation analyses conducted suggest that CSC01 formed a stable complex with KRAS-G13D. CSC01, through a dynamic protein-ligand interaction profiling analysis, was also shown to maintain strong interactions with the mutated aspartic acid residue throughout the simulation. Although binding free energy analysis through the umbrella sampling approach suggested that the affinity of CSC01 with the switch II pocket of KRAS-G13D is moderate, our DFT analysis showed that the stable interaction of the compound might be facilitated by the existence of favorable molecular electrostatic potentials. Furthermore, based on ADMET predictions, CSC01 demonstrated a satisfactory drug likeness and toxicity profile, making it an exemplary candidate for consideration as a potential KRAS-G13D inhibitor.

Antibiotic resistance in the aquatic environment: Analytical techniques and interactive impact of emerging contaminants.

Antibiotic pollution is becoming an increasingly severe threat globally. Antibiotics have emerged as a new class of environmental pollutants due to their expanding usage and indiscriminate application in animal husbandry as growth boosters. Contamination of aquatic ecosystems by antibiotics can have a variety of negative impacts on the microbial flora of these water bodies, as well as lead to the development and spread of antibiotic-resistant genes. Various strategies for removing antibiotics from aqueous systems and environments have been developed. Many of these approaches, however, are constrained by their high operating costs and the generation of secondary pollutants. This review aims to summarize research on the distribution and effects of antibiotics in aquatic environments, their interaction with other emerging contaminants, and their remediation strategy. The ecological risks associated with antibiotics in aquatic ecosystems and the need for more effective monitoring and detection system are also highlighted.