1. A novel inhibitor of human La protein with anti-HBV activity discovered by structure-based virtual screening and in vitro evaluation.
- Author
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Jing Tang, Zhi-Min Huang, Ying-Yi Chen, Zhao-Hui Zhang, Gao-Lin Liu, and Jian Zhang
- Subjects
Medicine ,Science - Abstract
BACKGROUND: Over 350 million people worldwide are infected with hepatitis B virus (HBV), a major cause of liver failure and hepatocellular carcinoma. Current therapeutic agents are highly effective, but are also associated with development of viral resistance. Therefore, strategies for identifying other anti-HBV agents with specific, but distinctive mechanisms of action are needed. The human La (hLa) protein, which forms a stabilizing complex with HBV RNA ribonucleoprotein to promote HBV replication, is a promising target of molecular therapy. AIMS: This study aimed to discover novel inhibitors of hLa that could inhibit HBV replication and expression. METHODS: A multistage molecular docking approach was used to screen a Specs database and an in-house library against hLa binding sites. Sequential in vitro evaluations were performed to detect potential compounds with high scores in HepG2.2.15 cells. RESULTS: Of the 26 potential compounds with high scores chosen for experimental verification, 12 had HBV DNA inhibition ratios of less than 50% with P
- Published
- 2012
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