Structure-activity relationships of fluorene compounds inhibiting HCV variants
- Structure-activity relationships of fluorene compounds inhibiting HCV variants
- 배애님; 금교창; 가디 장데부 고라크스나트; 김희선; 유영수; 문재곤; 문희조; 코하라; 김병문; 장승기; Jae Seung Lee
- Hepatitis c virus; Direct-acting antiviral agent (DAA); NS5A inhibitor; Resistance-associated variant (RAV); Structure-activity relationship (SAR); Molecular docking
- Issue Date
- Antiviral research
- VOL 174, 104678
- Approximately 71 million people suffer from hepatitis C virus (HCV) infection worldwide. Persistent HCV infection causes liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma, resulting in approximately 400,000 deaths annually. Effective direct-acting antiviral agents (DAAs) have been developed and are currently used for HCV treatment targeting the following three proteins: NS3/4A proteinase that cleaves the HCV polyprotein into various functional proteins, RNA-dependent RNA polymerase (designated as NS5B), and NS5A, which is required for the formation of double membrane vesicles serving as RNA replication organelles. At least one compound inhibiting NS5A is included in current HCV treatment regimens due to the high efficacy and low toxicity of drugs targeting NS5A. Here we report fluorene compounds showing strong inhibitory effects on GT 1b and 3a of HCV. Moreover, some compounds were effective against resistance-associated variants to DAAs. The struc
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