Kim, Hee Sun You, Youngsu Mun, Jaegon Gadhe, Changdev G. Moon, Heejo Lee, Jae Seung Pae, Ae Nim Kohara, Michinori Keum, Gyochang Kim, Byeong Moon Jang, Sung Key 2024-01-19T18:04:46Z 2024-01-19T18:04:46Z 2021-09-04 2020-02 0166-3542 https://pubs.kist.re.kr/handle/201004/119031 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 structure-activity relationships of the compounds were analyzed. Furthermore, we investigated the molecular bases of the inhibitory activities of some compounds by the molecular docking method. English ELSEVIER HEPATITIS-C VIRUS NONSTRUCTURAL PROTEIN CRYSTAL-STRUCTURE RNA REPLICATION RESISTANCE DOMAIN Structure-activity relationships of fluorene compounds inhibiting HCV variants Article 10.1016/j.antiviral.2019.104678 1 ANTIVIRAL RESEARCH, v.174 ANTIVIRAL RESEARCH 174 scie scopus 000523596900022 2-s2.0-85076857208 Pharmacology & Pharmacy Virology Pharmacology & Pharmacy Virology Article HEPATITIS-C VIRUS NONSTRUCTURAL PROTEIN CRYSTAL-STRUCTURE RNA REPLICATION RESISTANCE DOMAIN Hepatitis c virus Direct-acting antiviral agent (DAA) NS5A inhibitor Resistance-associated variant (RAV) Structure-activity relationship (SAR) Molecular docking