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

  作者 LEE KYUNGAE; REN TAO; COTE MARCELINE; GHOLAMREZA BERAHMAN; MISASI JOHN; BRUCHEZ ANNA; CUNNINGHAM JAMES  
  选自 期刊  ACS Medicinal Chemistry Letters;  卷期  2013年4-2;  页码  239-243  
  关联知识点  
 

[摘要]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 antiviral 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 antiviral therapy.

 
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