1. Identification of natural compounds extracted from crude drugs as novel inhibitors of hepatitis C virus
- Author
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Yi Yan, Yingfang Li, Rui Guo, Shao-Jiang Song, Asako Murayama, Lusheng Que, Qing-Bo Liu, Hideki Aizaki, Masamichi Muramatsu, Hussein H. Aly, Ryosuke Suzuki, Kento Fukano, Takanobu Kato, Xin Zheng, Noriyuki Watanabe, Kousho Wakae, Xiao-Xiao Huang, Takaji Wakita, and Koichi Watashi
- Subjects
0301 basic medicine ,Hepatitis C virus ,Biophysics ,Hepacivirus ,Virus Replication ,medicine.disease_cause ,Antiviral Agents ,Biochemistry ,Crataegus ,Virus ,Subgenomic replicon ,03 medical and health sciences ,0302 clinical medicine ,Viral entry ,medicine ,Humans ,Medioresinol ,Molecular Biology ,Biological Products ,Plants, Medicinal ,biology ,Plant Extracts ,virus diseases ,Cell Biology ,biology.organism_classification ,Hepatitis C ,Virology ,digestive system diseases ,030104 developmental biology ,Drug development ,030220 oncology & carcinogenesis ,Oncovirus - Abstract
Natural product–derived crude drugs are expected to yield an abundance of new drugs to treat infectious diseases. Hepatitis C virus (HCV) is an oncogenic virus that significantly impacts public health. In this study, we sought to identify anti-HCV compounds in extracts of natural products. A total of 110 natural compounds extracted from several herbal medicine plants were examined for antiviral activity against HCV. Using a Huh7-mCherry-NLS-IPS reporter system for HCV infection, we first performed a rapid screening for anti-HCV compounds extracted from crude drugs. The compounds threo-2,3-bis(4-hydroxy-3-methoxyphenyl)-3-butoxypropan-1-ol (#106) and medioresinol (#110), which were extracted from Crataegus cuneate, exhibited anti-HCV activity and significantly inhibited HCV production in a dose-dependent manner. Analyses using HCV pseudoparticle and subgenomic replicon systems indicated that compounds #106 and #110 specifically inhibit HCV RNA replication but not viral entry or translation. Interestingly, compound #106 also inhibited the replication and production of hepatitis A virus. Our findings suggest that C. cuneate is a new source for novel anti-hepatitis virus drug development.
- Published
- 2021
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