Antiviral Activity of Extracts from Wild Grasses against Epstein-Barr Virus and Induction of Apoptosis in EBV-positive Lymphoblastoid Cells

Epstein-Barr virus (EBV) belongs to the human herpes virus family that infects more than 90% of the population. EBV is associated with a number of lymphoproliferative and autoimmune diseases. Use of the drugs, which would not only inhibit the reproduction of the virus, but also would stimulate the elimination of tumor cells, is important for the treatment of virus-associated tumors. In the current research the antiviral effects of the herbal extracts Proteflazid and Neoflazid were studied on the models of latent, acute and chronic EBV infections in Raji and B95-8 lymphoblastoid cells. Neoflazid was more toxic towards Raji cells than Proteflazid: the CC₅₀ indices were 8 µg/ml and 36 µg/ml respectively. Toxicities of these compounds in B95-8 cells were almost the same and their CC₅₀ indices were close to 25 µg/ml. Both drugs showed high antiviral activity against EBV lytic infection in Raji cells and EC₅₀ was 0.02 and 0.083 µg/ml for Proteflazid and Neoflazid, respectively, and selectivity indinces were 1800 and 96. They were less effective in B95-8 cells and even at a concentration of 10 µg/ml these compounds inhibited virus replication by only 10-19%.

We checked the ability of Proteflazid to induce apoptosis and found that the drug stimulated the apoptotic cell death in latent and lytic EBV infections at cytotoxic concentrations (30 µg/ml). The non-toxic concentration (5 µg/ml) induced apoptosis more actively (by 10%) during EBV lytic infection in cells B95-8 than in the case of latent infection in Raji cells.