Developing treatment for Epstein-Barr virus-related diseases.

Epstein-Barr virus (EBV) causes various diseases and it has been estimated that 2-3% of all cancers are caused by EBV. Other diseases include infectious mononucleosis. More recently, an association between EBV and multiple sclerosis has been demonstrated. Despite knowing that EBV causes disease for 60 years, there is no specific treatment for EBV. All EBV-infected cells express the protein EBNA1, which is essential for the virus, and knocking out EBNA1 also knocks out the virus. EBNA1 is therefore an interesting protein for the development of new treatment methods against EBV. Our research has shown that EBNA1 has a unique mechanism for regulating its own synthesis. We have shown the cellular mechanisms that regulate EBNA1 synthesis and we have identified compounds that specifically inhibit EBNA1 synthesis. We have also shown how these compounds work. Nasopharyngeal cancer (NPC) is a tumor that carries the virus in 100% of all cases. Treatment of two different NPC tumors in mice with anti-EBNA1 substances does not affect the animals significantly and there are no signs of toxicity but the tumors disappear. Substances that are more effective in inhibiting EBNA1 are more effective in preventing NPC tumor growth. A tumor that does not carry EBV (melanoma) is not affected by the treatment. This project aims to develop, in collaboration with medicinal chemists, new compounds that are effective in inhibiting EBNA1 synthesis and can be developed into drugs for EBV-associated diseases.