Two separate research teams have identified a critical protein in Ebola virus (EboV) infections. The discovery improves chances that drugs can be developed that directly combat Ebola infections, which cause severe hemorrhage, multiple organ failure and death.
Through a genome-wide genetic screen in human cells aimed at identifying molecules essential for Ebola’s virulence, Sean Whelan, Harvard Medical School, Boston, USA, and colleagues homed in on the endosomal membrane protein Niemann-Pick C1 (NPC1). Primarily associated with cholesterol metabolism, it causes a rare genetic disorder in children, Niemann-Pick disease, when mutated. This mutant form also completely blocks infection by the Ebola virus. Mice or cultured cells carrying a mutation in the NPC1 gene resisted Ebola infection.
James Cunningham and his group, Brigham and Women’s Hospital, Boston, USA, investigated Ebola by using a robotic method to screen tens of thousands of compounds. They identified a novel small molecule that inhibits Ebola virus entry into cells by more than 99 %. The inhibitor was used to investigate the Ebola infection pathway and found to target NPC1.
Small molecules that target NPC1 and inhibit Ebola virus infection have the potential to be developed into anti-viral drugs. While targeting NPC1 may also block the cholesterol transport pathway, short-term treatment would likely be tolerated.
- Ebola virus entry requires the cholesterol transporter Niemann–Pick C1,
Jan E. Carette, Matthijs Raaben, Anthony C. Wong, Andrew S. Herbert, Gregor Obernosterer, Nirupama Mulherkar, Ana I. Kuehne, Philip J. Kranzusch, April M. Griffin, Gordon Ruthel, Paola Dal Cin, John M. Dye, Sean P. Whelan, Kartik Chandran, Thijn R. Brummelkamp,
- Small molecule inhibitors reveal Niemann–Pick C1 is essential for Ebola virus infection,
Marceline Côté, John Misasi, Tao Ren, Anna Bruchez, Kyungae Lee, Claire Marie Filone, Lisa Hensley, Qi Li, Daniel Ory, Kartik Chandran, James Cunningham,