Development of new inhibitors for epstein-barr EBNA1 receptor dna-binding domain by molecular docking

Epstein-Barr virus (EBV), a member of human herpesvirus, causes infectious mononucleosis, Burkitt’s lymphoma, nasopharyngeal carcinoma, gastric carcinoma, and Hodgkin lymphomas. Epstein-Barr Nuclear Antigen 1 (EBNA1), one of antigens encoded by EBV, comprises of 641 amino acid residues. Among the latent infection EBNA1 acts in DNA replication, transcription of viral and cellular genes, and in immortilization of B-lymphocytes. These special roles of EBNA1 makes it an important drug target. In this study, we create a ligand set consit of totally 2068 ligands. 58 ligands were selected from literatures, while 1600 ligands downloaded from ZINC15 ligand database and 410 ligands designed by Breed, a software included in Schrodinger sowtware suite. Autodock4 docking software was used for molecular docking process. By filtering ligands according to their druggabilities totally 1635 ligands succesfully docked to EBNA1 crystal structure. Analyzes of docking results showed that B288 is the best scored ligand for DNA binding site of EBNA1. Totally 6 ligands scored less than -10.00 kcal/mol, where four of them were designed by Breed and 2 of them were from ZINC15 ligand database. It also has determined that residues located in DNA binding sites were involved in interactions with ligands.