Structure based Pharmacophore Modeling and Molecular Docking Studies of Kaposi's Sarcoma-Associated Herpes Virus (KSHV) Protease-A Therapeutic Drug Target

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) belongs to the gamma herpes virus subfamily, which is mainly associated with three types of malignancies which include Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. In the present study, energy-based pharmacophore modeling and molecular docking studies were performed for known KSHV protease inhibitors. Developed pharmacophore model was refined manually by mapping with the active site residues of KSHV protease. The refined pharmacophore model has one H-bond acceptor, three-ring aromatic (RA) and one hydrophobic (HY) groups (ARRRH). The ARRRH was taken for screening the KEGG natural compound database. Eight compounds were obtained from pharmacophore based screening. Out of eight, one compound namely Ginkgetin mapped well in the binding site with fitness score of > 1.5. The docking results showed that Ginkgetin bound at the conserved a conserved aromatic hot spot of human herpesvirus proteases with high glide score compared with known KSHV inhibitor. Hence this study is useful for further development of new and broad spectrum KSHV proteases inhibitors.