PBDE: structure-activity studies for the inhibition of hepatitis C virus NS3 helicase.
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.
Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. salam_bio26@yahoo.com.
Kazi Abdus
KA
Salam
Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan. atsushi.5961@ruri.waseda.jp.
Atsushi
A
Furuta
Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan. noda-naohiro@aist.go.jp.
Naohiro
N
Noda
Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan. stsuneda@waseda.jp.
Satoshi
S
Tsuneda
Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan. y.sekiguchi@aist.go.jp.
Yuji
Y
Sekiguchi
Department of Microbiology, Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi 409-3898, Japan. atsuyay@yamanashi.ac.jp.
Atsuya
A
Yamashita
Department of Microbiology, Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi 409-3898, Japan. kmoriishi@yamanashi.ac.jp.
Kohji
K
Moriishi
Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan. nakakoshi@phar.toho-u.ac.jp.
Masamichi
M
Nakakoshi
Research Institute for Environmental Management Technology, National Institute of Advanced Industrial Science and Technology (AIST), 16-1, Onogawa, Tsukuba, Ibaraki 305-8569, Japan. h.tani@aist.go.jp.
Hidenori
H
Tani
Department of Chemistry, Biology and Marine Science, University of the Ryukyus, Nishihara, Okinawa 903-0213, Japan. sonarroy@gmail.com.
Sona Rani
SR
Roy
Department of Chemistry, Biology and Marine Science, University of the Ryukyus, Nishihara, Okinawa 903-0213, Japan. jtanaka@sci.u-ryukyu.ac.jp.
Junichi
J
Tanaka
Institute of Medical Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan. tsubuki@hoshi.ac.jp.
Masayoshi
M
Tsubuki
Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. akimitsu@ric.u-tokyo.ac.jp.
Nobuyoshi
N
Akimitsu
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000818:Animals; D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D055768:Halogenated Diphenyl Ethers / Q000302:isolation & purification / Q000494:pharmacology*; D016174:Hepacivirus / Q000737:chemistry / Q000201:enzymology; D006801:Humans; D011161:Porifera / Q000737:chemistry*; D020365:RNA Helicases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000251:Adenosine Triphosphatases; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D055768:Halogenated Diphenyl Ethers; D020365:RNA Helicases; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases