Inhibition of Ebola Virus Infection: Identification of Niemann-Pick C1 as the Target by Optimization of a Chemical Probe
ACS Medicinal Chemistry Letters2012Vol. 4(2), pp. 239–243
Citations Over TimeTop 15% of 2012 papers
Kyung‐Ae Lee, Tao Ren, Marceline Côté, Berahman Gholamreza, John Misasi, Anna Bruchez, James M. Cunningham
Abstract
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.
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