Two-Pore Channels (TPCs) in Host Endosomes Are Critical to Ebola Virus Infectivity; Inhibiting These TPCs with Existing Drug May Prevent Ebola Infection

Dr. Robert Davey, Scientist and Ewing Halsell Scholar in the Department of Immunology and Virology at Texas Biomedical Research Institute, announced on February 26, 2015, that a small molecule called Tetrandrine, derived from an Asian herb, has shown to be a potent small molecule inhibiting infection of human white blood cells in in vitro experiments and prevented Ebola virus disease in mice. Tetrandine is currently approved for use in humans as a blood pressure medication. In their new work, the scientists found that Ebola virus entry into host cells requires the endosomal calcium channels called “two-pore channels” (TPCs). Disrupting TPC function by gene knockout, small interfering RNAs, or small molecule inhibitors halted virus trafficking and prevented infection. Tetrandrine, the most potent small molecule the scientists tested, inhibited infection of human macrophages, the primary target of Ebola virus in vivo, and also showed therapeutic efficiency in mice. The scientists concluded that TPC proteins play a key role in Ebola virus infection and may be effective targets for anti-viral therapy. The work will be reported on February 27, 2015 in Science in an article entitled “Two-Pore Channels Control Ebola Virus Host Cell Entry and Are Drug Targets for Disease Treatment.” The latest outbreak of Ebola virus disease has caused the death of more than 9,400 people worldwide and created an international crisis that has shown few signs of stopping, continuing to infect thousands in West Africa. Ebola virus causes hemorrhagic fever in humans and currently has no approved therapy or vaccine. Scientists at Texas Biomed have been working in the Institute's Biosafety Level 4 containment laboratory for more than ten years to find a vaccine, therapies, and detection methods for the virus. Dr.
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