Tetrandrine derived from Chinese herb blocks Ebola infection in mice

The Ebola outbreak in West Africa highlights the need for anti-Ebola drugs. In a new study published in the journal Science[1], an alkaloid called tetrandrine derived from Chinese herb blocked Ebola infection in mice.

Scientists found that Ebola virus entry into host cells requires the endosomal calcium channels called two-pore channels (TPCs). The Ebola virus could not enter cells lacking TPCs or cells treated with a TPC inhibitor. Ebola virus initiates host cell entry by first binding to several types of cell surface proteins. Then the virus is taken into the cell in structures called endosomes. TPCs in endosomes control the movement of endosomes containing virus particles.

The authors tested a few existing calcium channel blockers and found tetrandrine was especially potent, with an IC50 of 55 nM. When the drug (90 mg/kg, QOD) was given to mice who had been given a lethal dose of Ebola the day before, half of the mice survived.

Tetrandrine is only approved in China for the treatment of pain, lung cancer, and silicosis at the dose of 60-300 mg/day. The anti-Ebola dose in humans equivalent to the one given to the mice would be 500 mg or more. I hope the dose needed to control Ebola will be safe.

Prof. Norbert Klugbauer, a co-author, said “tetrandrine is now one of the most promising candidates that could be used to inhibit Ebola virus infection”. The next step is to test the drug in non-human primates.

A big concern is that the effectiveness of tetrandrine was reduced when the treatment was delayed by a single day. Anyway, the identification of tetrandrine as an anti-Ebola drug is significant. The paper explained the mechanism behind the survival effect, which is a crucial step if you want to make better drugs. Moreover, it is likely that all filoviruses require TPCs to infect cells and that tetrandrine is a broad -spectrum filovirus inhibitor.

[1] Science. 2015, 347(6225), 995-998.


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