title: Inhibition of Ebola Virus Infection: Identification of Niemann-Pick C1 as the Target by Optimization of a Chemical Probe.
abstract: A high throughput screen identified adamantane dipeptide1as an inhibitor of Ebola virus (EboV) infection. Hit-to-lead optimization to determine the structure-activity relationship (SAR) identified the more potent EboV inhibitor2and a photoaffinity labeling agent3. These anti-viral compounds were employed to identify the target as Niemann-Pick C1 (NPC1), a host protein that binds the EboV glycoprotein and is essential for infection. These studies establish NPC1 as a promising target for anti-viral therapy.
authors.affiliation: New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Kyungae
authors.initials: K
authors.lastname: Lee
authors.forename: Tao
authors.initials: T
authors.lastname: Ren
authors.forename: Marceline
authors.initials: M
authors.lastname: Côté
authors.forename: Berahman
authors.initials: B
authors.lastname: Gholamreza
authors.forename: John
authors.initials: J
authors.lastname: Misasi
authors.forename: Anna
authors.initials: A
authors.lastname: Bruchez
authors.forename: James
authors.initials: J
authors.lastname: Cunningham
keywords: Ebola virus; Niemann-Pick C1; photoaffinity label; small molecule inhibitor; target identification; viral entry