A German-American research team has succeeded in adding another crucial detail of how the fatal Ebola virus infects cells- and at the same time providing another approach for a possible therapy. Pharmacology professors Martin Biel and Christian Wahl of the Ludwig Maximilian University (LMU) and virologist Dr. Robert Davey from the Texas Biomedical Research Institute in San Antonio, USA, reported the results of their research in the February issue of the scientific journal, Science.

The deadly Ebola virus disease (EBV), previously known as Ebola hemorrhagic fever, is a serious and often fatal disease in humans, with a fatality rate of about 50%. The first outbreak, recorded in remote villages of Central Africa, occurred in 1976. More recently, a new outbreak spanning across both urban and rural areas of West Africa has arisen, with the first incidents recorded in March 2014. This current outbreak is the most complex and largest EBV outbreak to face mankind since 1976. To date, scientists have been struggling to develop a drug or vaccine that would treat or prevent EBV.

In order to infect host cell, the Ebola virus initially has to dock certain receptors present on the surface of certain cells, mainly macrophages which are the scavenger cells of the immune system. This docking process triggers a chain of events: the cells surround the virus with protuberances and catch them in vesicles, which in turn merges with other vesicles called lysosomes. Specific ion channels called two pore channels (TPCs) play an important role in this merging process on the membranes of the vesicles. Researchers have now discovered that these channels are essential for the viral infection cycle and blocking TPCs disrupts the cycle, resulting in the viruses remaining trapped within the vesicles. Particularly effective proved the drug tetrandrine, an herbal alkaloid that has been used in traditional oriental medicine for a long time. In mice, tetrandrine prevented the infection of macrophages by the Ebola virus and also showed therapeutic effects, coupled with a comparatively low toxicity.

Currently, there is no approved treatment for EBV on the market. Therefore, targeting TPCs with drugs such as tetrandrine may help prevent Ebola infection in the future and open the door to other effective antiviral drugs.

References:
Sakurai et al.Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment. Science 27 February 2015: Vol. 347 no. 6225 pp. 995-998

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