Molecular and structural insights into carvacrol and thymol alkylated derivatives targeting WSSV and AHPND-causing...

The intensification of shrimp farming has increased the incidence of infectious diseases associated with environmental instability, particularly White Spot Syndrome Virus (WSSV) and acute hepatopancreatic necrosis disease (AHPND), caused by Vibrio parahaemolyticus, resulting in high mortality and significant economic impacts. Given the limited efficacy of available therapeutic approaches, the search for bioactive compounds of natural origin emerges as an innovative and sustainable strategy. In this study, carvacrol and thymol derivatives were investigated through computational screening against the target proteins PirB (V. parahaemolyticus) and thymidylate synthase (WSSV). The results revealed energetically favorable binding profiles and high conformational stability of the complexes with PirB, as established by cavity analyses, suggesting strong antibacterial inhibitory potential. Although the affinity parameters for thymidylate synthase indicate lower antiviral priority, the consistent overlap with the co-crystallized ligand supports the plausibility of relevant biological activity. Notably, the carvacrol and thymol derivatives CVC and TMC compounds exhibited superior performance, demonstrating greater structural stability and interaction robustness. Taken together, these findings highlight carvacrol and thymol derivatives particularly CVC and TMC as promising candidates, as they combine moderate binding affinity with consistent structural stability across the evaluated targets. These results provide a computational framework for the rational development of new therapeutic strategies in shrimp farming, contributing to more effective and sustainable approaches, while warranting further experimental validation.