Identification of Ellagic Acid from Plant Rhodiola rosea L. as an Anti-Ebola Virus Entry Inhibitor

The recent 2014–2016 West African Ebola virus epidemic underscores the need for the development of novel anti-Ebola therapeutics, due to the high mortality rates of Ebola virus infections and the lack of FDA-approved vaccine or therapy that is available for the prevention and treatment. Traditional...

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Main Authors: Qinghua Cui, Ruikun Du, Manu Anantpadma, Adam Schafer, Lin Hou, Jingzhen Tian, Robert A. Davey, Han Cheng, Lijun Rong
Format: Article
Language:English
Published: MDPI AG 2018-03-01
Series:Viruses
Subjects:
Online Access:http://www.mdpi.com/1999-4915/10/4/152
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author Qinghua Cui
Ruikun Du
Manu Anantpadma
Adam Schafer
Lin Hou
Jingzhen Tian
Robert A. Davey
Han Cheng
Lijun Rong
author_facet Qinghua Cui
Ruikun Du
Manu Anantpadma
Adam Schafer
Lin Hou
Jingzhen Tian
Robert A. Davey
Han Cheng
Lijun Rong
author_sort Qinghua Cui
collection DOAJ
description The recent 2014–2016 West African Ebola virus epidemic underscores the need for the development of novel anti-Ebola therapeutics, due to the high mortality rates of Ebola virus infections and the lack of FDA-approved vaccine or therapy that is available for the prevention and treatment. Traditional Chinese medicines (TCMs) represent a huge reservoir of bioactive chemicals and many TCMs have been shown to have antiviral activities. 373 extracts from 128 TCMs were evaluated using a high throughput assay to screen for inhibitors of Ebola virus cell entry. Extract of Rhodiola rosea displayed specific and potent inhibition against cell entry of both Ebola virus and Marburg virus. In addition, twenty commercial compounds that were isolated from Rhodiola rosea were evaluated using the pseudotyped Ebola virus entry assay, and it was found that ellagic acid and gallic acid, which are two structurally related compounds, are the most effective ones. The activity of the extract and the two pure compounds were validated using infectious Ebola virus. The time-of-addition experiments suggest that, mechanistically, the Rhodiola rosea extract and the effective compounds act at an early step in the infection cycle following initial cell attachment, but prior to viral/cell membrane fusion. Our findings provide evidence that Rhodiola rosea has potent anti-filovirus properties that may be developed as a novel anti-Ebola treatment.
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spelling doaj.art-42aeef8a6ba540aeb112ba13acc8a22e2022-12-21T19:30:46ZengMDPI AGViruses1999-49152018-03-0110415210.3390/v10040152v10040152Identification of Ellagic Acid from Plant Rhodiola rosea L. as an Anti-Ebola Virus Entry InhibitorQinghua Cui0Ruikun Du1Manu Anantpadma2Adam Schafer3Lin Hou4Jingzhen Tian5Robert A. Davey6Han Cheng7Lijun Rong8College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, ChinaCollege of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, ChinaDepartment of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, TX 78227, USADepartment of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USACollege of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, ChinaCollege of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, ChinaDepartment of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, TX 78227, USADepartment of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USADepartment of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USAThe recent 2014–2016 West African Ebola virus epidemic underscores the need for the development of novel anti-Ebola therapeutics, due to the high mortality rates of Ebola virus infections and the lack of FDA-approved vaccine or therapy that is available for the prevention and treatment. Traditional Chinese medicines (TCMs) represent a huge reservoir of bioactive chemicals and many TCMs have been shown to have antiviral activities. 373 extracts from 128 TCMs were evaluated using a high throughput assay to screen for inhibitors of Ebola virus cell entry. Extract of Rhodiola rosea displayed specific and potent inhibition against cell entry of both Ebola virus and Marburg virus. In addition, twenty commercial compounds that were isolated from Rhodiola rosea were evaluated using the pseudotyped Ebola virus entry assay, and it was found that ellagic acid and gallic acid, which are two structurally related compounds, are the most effective ones. The activity of the extract and the two pure compounds were validated using infectious Ebola virus. The time-of-addition experiments suggest that, mechanistically, the Rhodiola rosea extract and the effective compounds act at an early step in the infection cycle following initial cell attachment, but prior to viral/cell membrane fusion. Our findings provide evidence that Rhodiola rosea has potent anti-filovirus properties that may be developed as a novel anti-Ebola treatment.http://www.mdpi.com/1999-4915/10/4/152EbolaMarburgRhodiola roseaellagic acidgallic acidTraditional Chinese medicine
spellingShingle Qinghua Cui
Ruikun Du
Manu Anantpadma
Adam Schafer
Lin Hou
Jingzhen Tian
Robert A. Davey
Han Cheng
Lijun Rong
Identification of Ellagic Acid from Plant Rhodiola rosea L. as an Anti-Ebola Virus Entry Inhibitor
Viruses
Ebola
Marburg
Rhodiola rosea
ellagic acid
gallic acid
Traditional Chinese medicine
title Identification of Ellagic Acid from Plant Rhodiola rosea L. as an Anti-Ebola Virus Entry Inhibitor
title_full Identification of Ellagic Acid from Plant Rhodiola rosea L. as an Anti-Ebola Virus Entry Inhibitor
title_fullStr Identification of Ellagic Acid from Plant Rhodiola rosea L. as an Anti-Ebola Virus Entry Inhibitor
title_full_unstemmed Identification of Ellagic Acid from Plant Rhodiola rosea L. as an Anti-Ebola Virus Entry Inhibitor
title_short Identification of Ellagic Acid from Plant Rhodiola rosea L. as an Anti-Ebola Virus Entry Inhibitor
title_sort identification of ellagic acid from plant rhodiola rosea l as an anti ebola virus entry inhibitor
topic Ebola
Marburg
Rhodiola rosea
ellagic acid
gallic acid
Traditional Chinese medicine
url http://www.mdpi.com/1999-4915/10/4/152
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