Bioactivity-guided screening identifies pheophytin a as a potent anti-hepatitis C virus compound from Lonicera hypoglauca Miq.

Sheng Yang Wang; Ching Ping Tseng; Keng Chang Tsai; Chia Fan Lin; Ching Ya Wen; Hsin Sheng Tsay; Naoya Sakamoto; Chin Hsiao Tseng; Ju Chien Cheng

doi:10.1016/j.bbrc.2009.05.043

Bioactivity-guided screening identifies pheophytin a as a potent anti-hepatitis C virus compound from Lonicera hypoglauca Miq.

Sheng Yang Wang, Ching Ping Tseng, Keng Chang Tsai, Chia Fan Lin, Ching Ya Wen, Hsin Sheng Tsay, Naoya Sakamoto, Chin Hsiao Tseng, Ju Chien Cheng^*

^*Corresponding author for this work

Department of Medical Biotechnology and Laboratory Science

Research output: Contribution to journal › Journal Article › peer-review

43 Scopus citations

Abstract

Chronic hepatitis C virus (HCV) infection is a worldwide public issue. In this study, we performed bioactivity-guided screening of the Lonicera hypoglauca Miq. crude extracts to find for naturally chemical entities with anti-HCV activity. Pheophytin a was identified from the ethanol-soluble fraction of L. hypoglauca that elicited dose-dependent inhibition of HCV viral proteins and RNA expression in both replicon cells and cell culture infectious system. Computational modeling revealed that pheophytin a can bind to the active site of HCV-NS3, suggesting that NS3 is a potent molecular target of pheophytin a. Biochemical analysis further revealed that pheophytin a inhibited NS3 serine protease activity with IC₅₀ = 0.89 μM. Notably, pheophytin a and IFNα-2a elicited synergistic anti-HCV activity in replicon cells with no significant cytotoxicity. This study thereby demonstrates for the first time that pheophytin a is a potent HCV-NS3 protease inhibitor and offers insight for development of novel anti-HCV regimens.

Original language	English
Pages (from-to)	230-235
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	385
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2009.05.043
State	Published - 24 07 2009

Keywords

Hepatitis C virus
Lonicera hypoglauca Miq.
Pheophytin a
Replicon cells

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbrc.2009.05.043

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title = "Bioactivity-guided screening identifies pheophytin a as a potent anti-hepatitis C virus compound from Lonicera hypoglauca Miq.",

abstract = "Chronic hepatitis C virus (HCV) infection is a worldwide public issue. In this study, we performed bioactivity-guided screening of the Lonicera hypoglauca Miq. crude extracts to find for naturally chemical entities with anti-HCV activity. Pheophytin a was identified from the ethanol-soluble fraction of L. hypoglauca that elicited dose-dependent inhibition of HCV viral proteins and RNA expression in both replicon cells and cell culture infectious system. Computational modeling revealed that pheophytin a can bind to the active site of HCV-NS3, suggesting that NS3 is a potent molecular target of pheophytin a. Biochemical analysis further revealed that pheophytin a inhibited NS3 serine protease activity with IC50 = 0.89 μM. Notably, pheophytin a and IFNα-2a elicited synergistic anti-HCV activity in replicon cells with no significant cytotoxicity. This study thereby demonstrates for the first time that pheophytin a is a potent HCV-NS3 protease inhibitor and offers insight for development of novel anti-HCV regimens.",

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author = "Wang, {Sheng Yang} and Tseng, {Ching Ping} and Tsai, {Keng Chang} and Lin, {Chia Fan} and Wen, {Ching Ya} and Tsay, {Hsin Sheng} and Naoya Sakamoto and Tseng, {Chin Hsiao} and Cheng, {Ju Chien}",

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AU - Wang, Sheng Yang

AU - Tseng, Ching Ping

AU - Tsai, Keng Chang

AU - Lin, Chia Fan

AU - Wen, Ching Ya

AU - Tsay, Hsin Sheng

AU - Sakamoto, Naoya

AU - Tseng, Chin Hsiao

AU - Cheng, Ju Chien

PY - 2009/7/24

Y1 - 2009/7/24

N2 - Chronic hepatitis C virus (HCV) infection is a worldwide public issue. In this study, we performed bioactivity-guided screening of the Lonicera hypoglauca Miq. crude extracts to find for naturally chemical entities with anti-HCV activity. Pheophytin a was identified from the ethanol-soluble fraction of L. hypoglauca that elicited dose-dependent inhibition of HCV viral proteins and RNA expression in both replicon cells and cell culture infectious system. Computational modeling revealed that pheophytin a can bind to the active site of HCV-NS3, suggesting that NS3 is a potent molecular target of pheophytin a. Biochemical analysis further revealed that pheophytin a inhibited NS3 serine protease activity with IC50 = 0.89 μM. Notably, pheophytin a and IFNα-2a elicited synergistic anti-HCV activity in replicon cells with no significant cytotoxicity. This study thereby demonstrates for the first time that pheophytin a is a potent HCV-NS3 protease inhibitor and offers insight for development of novel anti-HCV regimens.

AB - Chronic hepatitis C virus (HCV) infection is a worldwide public issue. In this study, we performed bioactivity-guided screening of the Lonicera hypoglauca Miq. crude extracts to find for naturally chemical entities with anti-HCV activity. Pheophytin a was identified from the ethanol-soluble fraction of L. hypoglauca that elicited dose-dependent inhibition of HCV viral proteins and RNA expression in both replicon cells and cell culture infectious system. Computational modeling revealed that pheophytin a can bind to the active site of HCV-NS3, suggesting that NS3 is a potent molecular target of pheophytin a. Biochemical analysis further revealed that pheophytin a inhibited NS3 serine protease activity with IC50 = 0.89 μM. Notably, pheophytin a and IFNα-2a elicited synergistic anti-HCV activity in replicon cells with no significant cytotoxicity. This study thereby demonstrates for the first time that pheophytin a is a potent HCV-NS3 protease inhibitor and offers insight for development of novel anti-HCV regimens.

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KW - Lonicera hypoglauca Miq.

KW - Pheophytin a

KW - Replicon cells

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Bioactivity-guided screening identifies pheophytin a as a potent anti-hepatitis C virus compound from Lonicera hypoglauca Miq.

Abstract

Keywords

UN SDGs

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