Scientists identify potential drug target for deadly Ebola virus

Ebola virus entering cell

The Ebola virus entering a cell. Copyright Nature, 2011.

Viruses are dodgy—they can change quickly and sneak around the body undetected, making the prospect of finding and killing individual viral agents challenging. As a result, scientists have hypothesized that rather than trying to kill viruses directly, preventing them from entering our cells and replicating might represent a better therapeutic strategy.

In the first step towards developing such a drug for the Ebola virus—one of the deadliest known viruses infecting humans—Whitehead Institute researchers have determined exactly how Ebola enters and infects our cells.

In work published last month in Nature, former Whitehead Institute Fellow Thijn Brummelkamp discovered that the Ebola virus uses a cholesterol transport protein to enter a cell’s cytoplasm for replication and infection. By suppressing the gene that codes for this particular protein (the gene is known as NPC1), researchers can prevent the protein from being produced and thus the virus from ever utilizing it.

To test these results in a living system, collaborators at the U.S. Army Medical Research Institute of Infectious Diseases examined the effects of active Ebola virus on mice that had one copy of the NPC1 gene knocked out. Control mice, with two functioning copies of the NPC1 gene, quickly succumbed to infection, while the NPC1 knockout mice were largely protected from the virus.

“This is pretty unexpected,” says Jan Carette, a co-author of this study and former postdoctoral researcher at Whitehead Institute. “Now that we know that NPC1 is an Ebola virus host factor, it provides a strong platform from which to start developing new antivirals.”