Bioinformatic Approaches for Targeting Drug Resistance Mechanisms in Gastrointestinal Nematodes: A Systematic Review

Background: The increasing resistance of gastrointestinal nematodes to common anthelmintic drugs poses a serious threat to animal health and the economic viability of livestock farming worldwide. This challenge requires an urgent need to identify and develop new therapeutic agents. The approach of using small, safe molecules is promising due to their lower toxicity profile and rational design capabilities. This systematic review aims to examine and integrate key bioinformatics applications to accelerate the discovery and development of these molecules to combat drug resistance in gastrointestinal nematodes. Methods: This study used a systematic review and conducted a comprehensive search across reputable scientific databases, including PubMed, Scopus, Web of Science, and Google Scholar. The search time frame was set to January ۲۰۲۰ to August ۲۰۲۵. The keywords used included combinations of “bioinformatics”, “gastrointestinal nematodes”, “anthelmintic resistance”, “small molecule”, “virtual screening”, and “new drug”. Inclusion criteria were original studies that specifically addressed the use of computational tools in targeting nematodes. After title and abstract screening, full text evaluation and data extraction were performed according to a predefined protocol. Results: Analysis of ۱۷ eligible studies demonstrated the pivotal role of bioinformatics in several key areas. Sequencing and analysis of nematode genomes have identified essential and specific proteins (e.g., ion channels, metabolic enzymes) involved in resistance mechanisms, which are now being pursued as novel drug targets. Using molecular docking, large molecular libraries were screened against protein targets of resistant nematodes, and the most potent molecules with high binding affinity and selectivity were identified. Quantitative Structure-Activity Relationship (QSAR) and molecular dynamics simulation-based tools have been used to optimize the structures of lead molecules to improve potency, selectivity, and pharmacokinetic properties. Moreover, modeling potential mutations in drug targets that can confer resistance has led to the design of “resistance-breaking” molecules. Conclusion: The findings clearly demonstrate that bioinformatics has become an essential and transformative tool in the fight against anthelmintic resistance. By accelerating target identification, lead molecule discovery, and optimization, this technology has shortened and made more cost-effective the path to developing new, effective, and safe drugs against resistant gastrointestinal nematodes.

کلیدواژه ها:

Bioinformatics ، Gastrointestinal nematodes ، Anthelmintic resistance ، Safe small molecule ، Virtual screening