Discovery of Ebola virus' 'Achilles heel' may yield better cure

An international team including scientists from Albert Einstein College of Medicine of Yeshiva University and the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) has identified the molecular "lock" that the deadly Ebola virus must pick to gain entry to cells.

The findings suggest that drugs blocking entry to this lock could protect against Ebola infection.

The researchers found that the Ebola virus can't infect cells unless it first attaches to a host protein called Niemann-Pick C1 (NPC1) in membrane compartments called lysosomes deep within cells.

Associate professor and co-study leader Kartik Chandran, Ph.D., said that the mice study reveals NPC1 to be an Achilles' heel for Ebola virus infection. Mice lacking both copies of the NPC1 gene, and therefore devoid of the NPC1 protein, were completely resistant to infection.

The current animal study was aimed at confirming whether NPC1 is essential for Ebola infectivity. The researchers challenged both "wild type" mice (which have two intact copies of the NPC1 gene) and "knockout mice" (lacking both copies of the gene) with Ebola virus. While the wild type mice succumbed to the infection, the knockout mice were entirely free of virus replication and completely protected against the disease, said Dr. Walkley.

Senior research scientist Dr. Andrew S. Herbert, PhD, at USAMRIID, and co-first author of the study, said that even though such a treatment in humans would also block the cholesterol transport pathway, they think patients would be able to tolerate the treatment, which would be needed for only a short time.

Dr. Chandran said future research in humans, based on these findings, will lead to the development of antiviral drugs that can effectively target NPC1 and prevent infection not just by Ebola, but also by other highly virulent filoviruses, which also require NPC1 as a receptor.

The study is published in online journal mBio.