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ACS Med Chem Lett. 2013 Feb 14;4(2):239-243. Epub 2012 Dec 19.

Inhibition of Ebola Virus Infection: Identification of Niemann-Pick C1 as the Target by Optimization of a Chemical Probe.

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New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases, Harvard Medical School, Boston, Massachusetts 02115, USA.


A high throughput screen identified adamantane dipeptide 1 as an inhibitor of Ebola virus (EboV) infection. Hit-to-lead optimization to determine the structure-activity relationship (SAR) identified the more potent EboV inhibitor 2 and a photoaffinity labeling agent 3. 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.


Ebola virus; Niemann-Pick C1; photoaffinity label; small molecule inhibitor; target identification; viral entry

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