Effective natural inhibitors targeting IL-2 receptor by computational study
Yuanyuan Hou, Yanhao Mou, Haoqun Xie, Gaojing Dou, Junliang Ge, Sheng Zhong · Research Square · 2022
Abstract Objective: This study aims to screen ideal lead compounds and potential candidate drugs with inhibitory effect on IL-2R from the drug library (ZINC database).Methods: Computer Aided virtual technology was used to identify the potential inhibitors of IL-2R. Libdock is used for structure based screening, followed by ADME (absorption, distribution, metabolism and excretion) and toxicity prediction. Molecular docking was performed to demonstrate the binding affinity mechanism between ligand and IL-2R. Molecular dynamics simulations were used to evaluate the stability of ligand receptor complexes.Results: Two effective natural compounds ZINC00044361247 and ZINC0028882432 were found in ZINC database to bind to IL-2R, showing high binding affinity. In addition, they were predicted to have low rodent carcinogenicity, Ames mutagenicity, developmental toxicity potential and high tolerance to cytochrome P4502D6. Molecular dynamics simulation shows that ZINC00044361247 and ZINC0028882432 and IL-2R have more favorable potential energy and can exist stably in the natural environment.Conclusion: This study shows that ZINC00044361247 and ZINC0028882432 are ideal IL-2R targeted inhibitors. These compounds are safe potential drug candidates and are of great significance in inhibiting T cell-mediated immune response and allogeneic transplantation.