Calcium Channel Fingered In Ebola’s Infection Pathway

A critical step in the path the Ebola virus takes to infect host cells has been elucidated. Scientists found the virus requires a specific calcium channel to release its viral genome into a host cell. The researchers could block this process with tetrandrine, a drug used in China to treat high blood pressure, suggesting a possible Ebola virus therapy.

Robert A. Davey, of the Texas Biomedical Research Institute, in San Antonio, had long suspected that calcium signaling channels were crucial to the Ebola virus’s infection process. Now, he and an international team of researchers have identified two-pore channel 2 (TPC2) as key (Science 2015, DOI: 10.1126/science.1258758).

TPC2 channels are found in a cell’s endosomes—the cellular sorting compartments that break down proteins for recycling. These calcium channels control the way endosomes move through cells. Ebola viruses pop up in endosomes after host cells engulf them whole.

The researchers found that mice genetically engineered to not have TPC2 evaded Ebola infection. In normal mice and in cell culture, the small-molecule TPC2 blocker tetrandrine stopped virus trafficking. Davey tells C&EN that his team is currently looking at tetrandrine derivatives to see if they can also halt the virus.

Darryl Falzarano, an infectious disease expert at Canada’s Vaccine & Infectious Disease Organization-International Disease Centre, who studies Ebola virus, says the finding is exciting from a basic research perspective. “Ebola clearly undergoes a complex series of steps in its entry pathway, and defining the cellular requirements for this process may one day lead to novel targets for intervention,” he says.

Falzarano cautions, however, that the finding won’t lead to immediate new Ebola therapies. Tetrandrine isn’t approved for use in humans outside China and faces a long slog through the regulatory process. Also, he suspects it might be better as a prophylactic Ebola treatment than one for people already infected with the virus. Tetrandrine or a derivative eventually may be part of a combination Ebola therapy, Falzarano says, “but this would be a considerable time in the future.”