期刊
ACS MEDICINAL CHEMISTRY LETTERS
卷 4, 期 2, 页码 239-243出版社
AMER CHEMICAL SOC
DOI: 10.1021/ml300370k
关键词
Ebola virus; small molecule inhibitor; viral entry; photoaffinity label; target identification; Niemann-Pick C1
资金
- NIH [U54 AI057159 (NERCE/BEID), K08AI079381]
- PIDS-Sanofi-Pasteur
- Stena Foundation
- Fonds de la Recherche en Sante du Quebec
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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