Recently, Dr Cheng Luo from Prof. Hua-liang Jiang’s team in Shanghai Institute of Materia Medica and Paul M. Lieberman from Wistar Institute of University of Pennsylvania collaboratively discovered a series of small molecules that can inhibit EBNA1-DNA binding activity, thereby blocking EBV replication functions for the first time. This study was published on PLoS ONE [5(4): e10126. doi:10.1371/journal.pone.0010126] on 12 April 2010.

Epstein-Barr virus（EBV) latent infection can induce the Burkitt's lymphoma, nasopharyngeal carcinoma, gastric carcinoma, Hodgkin's disease lymphoma and other lymphoid and epithelial cell malignancies. On a global scale, there are more than 90% of people infected with EBV. Thus, EBV was listed as a human carcinogenic virus by the World Health Organization. So far, there is no efficacious drug or therapy for EBV latent infection or EBV-related diseases.

In this study, Dr Luo and his Ph.D. student Ning Li has formed a strategic partnership with professor Lieberman on the research of drug design, molecular cell biology and virology based on the crystal structure of EBNA1/DNA complex (EBV nuclear antigen 1). EBNA1 is an EBV-encoded DNA-binding protein expressed during all forms of EBV latency and tumor, and required for viral genome maintenance and the immortalization of primary Blymphocytes during latent infection. They successfully identified several new series of small molecules inhibit EBNA1-DNA binding in vitro and partially block EBNA1 function in vivo. Since this is the first demonstration that EBNA1 is an attractive candidate target for the treatment of EBV latent infection. Their study represents a first step in the prevention and treatment of most malignant tumors induced by EBV latency, and lays solid foundation for the development of specific drugs of EBNA1 and EBV latent infection. Furthermore, the study proves that the approach based on the structure of protein-DNA is promising for EBNA1, and is likely to be a feasible approach for other viral proteins with known X-ray crystal structures. It may accelerate the search of anti-viral compounds that target viral latent infection.

This study is funded by the People's Republic of China Ministry of Science and Technology, the National Natural Science Foundation of China and Shanghai Science and Technology Commission.

Source:Li N., Thompson S., Schultz D.C., Zhu W., Jiang H., Luo C.*, Lieberman P.M. *, Discovery of Selective Inhibitors Against EBNA1 via High Throughput In Silico Virtual Screening, PLoS ONE 2010, 5(4), e10126