Identification of Potent Lead Molecules for Furin Receptor Through HTVS and Molecular Docking

Objective: Furin is the family of proprotein convertase and localized in Trans Golgi Network (TGN) and cell surface. It is the major processing enzyme of the secretory pathway. Furin inhibitors are known to be therapeutic agents since it is involved in viral and bacterial activation, alzimer’s disease and cancer. Furin is the family of proprotein convertase and localized in Trans Golgi Network (TGN) and cell surface. It is the major processing enzyme of the secretory pathway. Furin inhibitors are known to be therapeutic agents since it is involved in viral and bacterial activation, alzimer’s disease and cancer. In this study, High Throughput virtual screening is used to screen natural and synthetic compounds and the short listed compounds are taken for checking the ADMET property. Methodology: The crystal structure of furin protein target was obtained from RCSB protein data bank (PDB Id: 4RYD) and protein preparation is done. Ligand from Zinc database are downloaded and prepared and taken for HTVS. Then the short listed compounds were taken for studying the ADMET property. Results: ZINC19799372, ZINC20411483, ZINC20412114, ZINC20411616 has highest docking score when compared with other small molecules. The drug-likeness and pharmacokinetic properties and other descriptors such as molecular weight, H-bond donors, H-bond acceptors, logP (octanol/water) and human oral absorption for the screened hits were predicted by Qikprop. The selected screened compounds ZINC19799372, ZINC20411483, ZINC20412114, ZINC20411616 has satisfactory percentage of oral absorption of >80% and are known to be potential lead compounds. Conclusion: In this study, we have screened the dataset of 1000 natural compounds and predicted the drug-likeness properties to identify the potent inhibitors against furin, and were also able to visualize the interactions of protein-ligand complex.