PBDE: Structure-Activity Studies for the Inhibition of Hepatitis C Virus NS3 Helicase

• Main Authors: Kazi Abdus Salam, Atsushi Furuta, Naohiro Noda, Satoshi Tsuneda, Yuji Sekiguchi, Atsuya Yamashita, Kohji Moriishi, Masamichi Nakakoshi, Hidenori Tani, Sona Rani Roy, Junichi Tanaka, Masayoshi Tsubuki, Nobuyoshi Akimitsu
• Format: Article
• Language: English
• Published: MDPI AG 2014-04-01
• Series: Molecules
• Subjects: hepatitis C virus; NS3 RNA helicase; marine sponge; polybrominated diphenyl ether
• Online Access: http://www.mdpi.com/1420-3049/19/4/4006
• ISSN: 1420-3049

The helicase portion of the hepatitis C virus nonstructural protein 3 (NS3) is considered one of the most validated targets for developing direct acting antiviral agents. We isolated polybrominated diphenyl ether (PBDE) 1 from a marine sponge as an NS3 helicase inhibitor. In this study, we evaluated the inhibitory effects of PBDE (1) on the essential activities of NS3 protein such as RNA helicase, ATPase, and RNA binding activities. The structure-activity relationship analysis of PBDE (1) against the HCV ATPase revealed that the biphenyl ring, bromine, and phenolic hydroxyl group on the benzene backbone might be a basic scaffold for the inhibitory potency.