2. Academic Validation
  3. 5-Oxo-1-[(2,3,6,7-tetramethoxy-9-phenanthrenyl)methyl]-L-proline Inhibits Hepatitis C Virus Entry

5-Oxo-1-[(2,3,6,7-tetramethoxy-9-phenanthrenyl)methyl]-L-proline Inhibits Hepatitis C Virus Entry

  • Sci Rep. 2019 May 13;9(1):7288. doi: 10.1038/s41598-019-43783-6.
Lap P Nguyen 1 2,  Chorong Park 2,  Trang T D Luong 2,  Eun-Mee Park 3,  Dong-Hwa Choi 4,  Kang Min Han 5,  Han N Mai 1 2,  Huu C Nguyen 1,  Yun-Sook Lim 6 7,  Soon B Hwang 8 9
Affiliations

Affiliations

  • 1 Laboratory of RNA Viral Diseases, Korea Zoonosis Research Institute, Chonbuk National University, Iksan, South Korea.
  • 2 National Research Laboratory of Hepatitis C Virus, Hallym University, Anyang, South Korea.
  • 3 Korea National Institute of Health, Cheongju, South Korea.
  • 4 Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
  • 5 Department of Pathology, Dongguk University Ilsan Hospital, Goyang, South Korea.
  • 6 Laboratory of RNA Viral Diseases, Korea Zoonosis Research Institute, Chonbuk National University, Iksan, South Korea. yunsolim@hanmail.net.
  • 7 National Research Laboratory of Hepatitis C Virus, Hallym University, Anyang, South Korea. yunsolim@hanmail.net.
  • 8 Laboratory of RNA Viral Diseases, Korea Zoonosis Research Institute, Chonbuk National University, Iksan, South Korea. sbhwang@jbnu.ac.kr.
  • 9 National Research Laboratory of Hepatitis C Virus, Hallym University, Anyang, South Korea. sbhwang@jbnu.ac.kr.
PMID: 31086268 DOI: 10.1038/s41598-019-43783-6
Abstract

Hepatitis C virus (HCV) is the major causative agent of chronic liver diseases, including liver cirrhosis and hepatocellular carcinoma. The recent development of highly effective direct-acting antivirals (DAAs) has revolutionized the treatment of HCV patients. However, these DAAs are exorbitantly expensive for the majority of HCV patients worldwide. Moreover, these drugs still show genotypic difference in cure rate and have some resistant-associated variants. Tylophorine, a natural compound derived from Tylophora indica Plants, is known to have anti-inflammatory and anti-cancerous growth activities. In the present study, we showed that two tylophorine intermediates, 5-Oxo-1-[(2,3,6,7-tetramethoxy-9-phenanthrenyl) methyl]-L-proline (O859585) and 2,3,6,7-tetramethoxy-9-phenanthrenecarboxylic acid (T298875), displayed anti-HCV activity with an EC50 of 38.25 µM for T298875 and 29.11~35.3 µM for O859585 in various HCV genotypes. We demonstrated that O859585 efficiently blocked HCV attachment by neutralizing free viral particles without affecting other stages of the HCV life cycle and interferon stimulation. O859585 interrupted binding between HCV E2 and CD81. Of note, co-treatment of O859585 with either interferon alpha (IFNα) or sofosbuvir exerted either an additive or synergistic Antiviral activity in HCV-infected cells with no measurable effect on cell viability. Most importantly, O859585 in combination with IFNα and sofosbuvir exhibited synergistic effects on anti-HCV activity in primary human hepatocytes. Collectively, these data suggest that O859585 may be a novel Antiviral agent for HCV therapy.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-15005
    99.97%, HCV 抑制剂
    HCV
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