(4R,6S)-2-Dihydromenisdaurilide is a Butenolide that Efficiently Inhibits Hepatitis C Virus Entry

Chueh Yao Chung, Ching Hsuan Liu, Guey Horng Wang, Alagie Jassey, Chia Lin Li, Lei Chen, Ming Hong Yen, Chun Ching Lin, Liang Tzung Lin

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Without a vaccine, hepatitis C virus (HCV) remains a significant threat, putting 170-300 million carriers worldwide at risk of cirrhosis and hepatocellular carcinoma. Although the direct-acting antivirals targeting HCV replication have revolutionized the treatment of hepatitis C, several obstacles persist, including resistance development, potential side-effects, and the prohibitive cost that limits their availability. Furthermore, treatment of HCV re-infection in liver transplantation remains a significant challenge. Developing novel antivirals that target viral entry could help expand the scope of HCV therapeutics and treatment strategies. Herein, we report (4R,6S)-2-dihydromenisdaurilide (DHMD), a natural butenolide, as an efficient inhibitor of HCV entry. Specifically, DHMD potently inhibited HCV infection at non-cytotoxic concentration. Examination on the viral life cycle demonstrated that DHMD selectively targeted the early steps of infection while leaving viral replication/translation and assembly/release unaffected. Furthermore, DHMD did not induce an antiviral interferon response. Mechanistic dissection of HCV entry revealed that DHMD could inactivate cell-free virus, abrogate viral attachment, and inhibit viral entry/fusion, with the most pronounced effect observed against the viral adsorption phase as validated using ELISA and confocal microscopy. Due to its potency, DHMD may be of value for further development as an entry inhibitor against HCV, particularly for application in transplant setting.

Original languageEnglish
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Jul 18 2016

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Virus Internalization
Hepacivirus
Antiviral Agents
Virus Diseases
butenolide
Therapeutics
Hepatitis C
Virus Replication
Life Cycle Stages
Confocal Microscopy
Liver Transplantation
Interferons
Adsorption
Dissection
Hepatocellular Carcinoma
Fibrosis
Vaccines
Enzyme-Linked Immunosorbent Assay
Viruses
Transplants

ASJC Scopus subject areas

  • General

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(4R,6S)-2-Dihydromenisdaurilide is a Butenolide that Efficiently Inhibits Hepatitis C Virus Entry. / Chung, Chueh Yao; Liu, Ching Hsuan; Wang, Guey Horng; Jassey, Alagie; Li, Chia Lin; Chen, Lei; Yen, Ming Hong; Lin, Chun Ching; Lin, Liang Tzung.

In: Scientific Reports, Vol. 6, 18.07.2016.

Research output: Contribution to journalArticle

Chung, Chueh Yao ; Liu, Ching Hsuan ; Wang, Guey Horng ; Jassey, Alagie ; Li, Chia Lin ; Chen, Lei ; Yen, Ming Hong ; Lin, Chun Ching ; Lin, Liang Tzung. / (4R,6S)-2-Dihydromenisdaurilide is a Butenolide that Efficiently Inhibits Hepatitis C Virus Entry. In: Scientific Reports. 2016 ; Vol. 6.
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