Ebola hemorrhagic fever (Ebola fever) is caused by a virus belonging to the family called Filoviridae, including BDBV, EBOV, RESTV, SUDV, and TAFV. The disease causes mortality rates as high as 90% and patients usually die from shock rather than from blood loss.
At the present, tyrosine kinase inhibitors including imatinib, dasatinib, and nilotinib, as effective agents, have been the first-line drugs against CML due to the advent of these targeted therapies. However, on clinical studies, resistance to Imatinib occurs frequently. Thus, it is needed to develop novel therapeutic agents that target signaling pathways other than Bcr/Abl for treatment of CML.
Icaritin is a hydrolytic product of icariin, which comes from the traditional Chinese herbal medicine Epimedium. Also, Icaritin can be synthesized from icariin by human intestinal bacteria in vitro. Previous studies have shown that icariin can induce liver cancer cell line apoptosis in vitro and suppress the adhesion and migration of gastric carcinoma cells.
The ZEBOV VP35 protein is a viral polymerase cofactor, and mediates immune evasion by antagonizing antiviral signaling pathways and is important for viral RNA synthesis. The further studies on mechanism indicate that the ZEBOV VP24 protein inhibits the cellular response to type I IFN by blocking the nuclear accumulation of phosphorylated STAT-1[1]. It is reported that the JAK-STAT pathway is the main type I IFNinduced signal transduction pathway, while the p38 mitogen-activated protein (MAP) kinase pathway is also important for the type I IFN response[2].
In the newest paper, Halfmann and the colleagues reported their results about the relationship between ZEBOV VP24 protein and MAPK signaling pathway. The data showed that IFN-beta induces p38 and the substrate ATF-2 phosphorylation in human embryonic kidney cells, and ZEBOV VP24 inhibits phosphorylation of p38 in IFN-betatreated cells, like the p38 inhibitor SB203580. And also phosphorylation of ATF-2 is inhibited by in human embryonic kidney cells treated with IFN-beta.
Taken together, ZEBOV VP24 protein can inhibit JAK-STAT pathway and MAPK signaling pathway, and thus Ebola VP35 represents a potential therapeutic target against ebola hemorrhagic fever.

References
[1]. J Virol 2006; 80:515667.
[2]. Nat Immunol 2005; 5:37586.

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Icaritin, a potential agent in the treatment of CML