Insilico identification of a ferroportin inhibitor for the management of iron-overload condition in Beta Thalassemia major patients.
Abstract The reason of high mortality rate in the patients of beta-thalassemia major is iron overload because it leads to many secondary complications. Condition of iron overload is known as hemochromatosis (HC). HC causes distorted formation of HFE protein that disturbs the whole pathway of HAMP protein synthesis which results in unbounded form of ferroportin and hence iron keeps absorbing in the body, leading to iron accumulation. The current study was conducted to identify a potential phytochemical that could bind to ferroportin and inhibits its iron absorbing activity within the body. The 3D structure of Ferroportin was unavailable in protein data bank PDB, therefore, it was developed by using different bioinformatics tools and best structure was identified through SAVES and RAMPAGE analysis. This best structure was docked with a library of 1010 bioactive phytochemicals by using MOE-2009 software. The top-ten ranked potential inhibitors were then evaluated for drug-like properties through molsoft and Molinspiration server followed by ADMET analysis. Our study demonstrated that “Taxifolin’ showed the maximum binding affinity with Ferroportin and also demonstrates maximum drug-like properties. Thus this compound could be used as a potential inhibitor of ferroportin. However, in-vitro and in-vivo studies must be conducted to validate the therapeutic potential of taxifolin against hemochromatosis.