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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 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.

SUBMITTER: Lee K

PROVIDER: S-EPMC3601783 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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

Lee Kyungae K Ren Tao T Côté Marceline M Gholamreza Berahman B Misasi John J Bruchez Anna A Cunningham James J

ACS medicinal chemistry letters 20121219 2

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 prom ...[more]

PMID: 23526644

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