Structure based drug designing against Inosine Monophosphate Dehydrogenase Receptor of Cryptosporidium parvum

摘要

An intracellular protozoan parasite, Cryptosporidium parvum diarrheal disease cryptosporidiosis in humans. In immunocompetent host, its infection is generally self-limiting gastroenteritis however for immunocompromised host (HIV/ AIDS patients) such infection can results in life-threatening diarrheal disease. The deliberate release of infective oocysts to contaminate water supplies placed Cryptosporidium a suitable agents for bio-terrorism. The only licensed drug, nitazoxanide is available to treat human cryptosporidiosis in immunocompetent patients but for young children and immunocompromised patients no therapy is available. In present study, we have selected Inosine 5'-monophosphate dehydrogenase (IMPDH) for treating Cryptosporidium infection. Cryptosporidium gene for IMPDH is totally different from mammalian because during course of evolution parasite obtained it from bacteria through lateral gene transfer. Small molecules that can inhibit the reaction catalysed by CpIMPDH would be better alternatives for treating cryptosporidiosis. The three dimensional structural coordinates of CpIMPDH protein retrieved from PDB database, has been subjected to virtual screening analysis against PubChem database to retrieve the ligands having high affinity towards CpIMPDH. Further molecular docking analysis was performed by using Autodock 4.0 after selecting ligands via SwissADME. Compounds having estimated free energy of binding from -6.44 kcal/mol to -6.12 kcal/mol were screened out as lead compounds. The lead molecules found have fulfilled ADME properties and were assumed to be potential anti-crytosporidial drug. This study would be a way to identify new therapeutics for cryptosporidium infection.