Computational tool for immunotoxic assessment of pyrethroids toward adaptive immune cell receptors

BACKGROUND: Pyrethroids have prominently known for their insecticidal actions worldwide, but recent reports as anticancer and antiviral applications gained a lot of interest to further understand their safety and immunotoxicity. OBJECTIVE: This encouraged us to carry out our present study to evaluate the interactions of pyrethroids toward adaptive immune cell receptors. MATERIALS AND METHODS: Type 1 and Type 2 pyrethroids were tested on T (CD4 and CD8) and B (CD28 and CD45) immune cell receptors using Maestro 9.3 (Schrödinger, LLC, Cambridge, USA). In addition, top-ranked tested ligands were too explored for toxicity prediction in rodents using ProTOX tool. RESULTS: Pyrethroids (specifically type 2) such as fenvalerate (−5.534 kcal/mol: CD8), fluvalinate (−4.644 and − 4.431 kcal/mol: CD4 and CD45), and cypermethrin (−3.535 kcal/mol: CD28) have outcome in less energy or more affinity for B-cell and T-cell immune receptors which may later result in the immunosuppressive and hypersensitivity reactions. CONCLUSION: The current findings have uncovered that there is a further need to assess the Type 2 pyrethroids with wet laboratory experiments to understand the chemical nature of pyrethroid-induced immunotoxicity. SUMMARY: Fenvalerate showed apex glide score toward CD8 immune receptor, while fluvalinate confirmed top-ranked binding with CD4 and CD45 immune proteins. In addition, cypermethrin outcame in top glide score against CD28 immune receptor. Top dock hits (Type 2) pyrethroids have shown probable toxicity targets toward AOFA: Amine oxidase (flavin-containing) A and PGH1: Prostaglandin G/H synthase 1, respectively. Abbreviations used: PDB: Protein Data Bank; AOFA: Amine oxidase (flavin-containing) A; PGH 1: Prostaglandin G/H synthase 1.