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Open Access Research article

Broad-spectrum antiviral activity of chebulagic acid and punicalagin against viruses that use glycosaminoglycans for entry

Liang-Tzung Lin12, Ting-Ying Chen3, Song-Chow Lin4, Chueh-Yao Chung5, Ta-Chen Lin6, Guey-Horng Wang7, Robert Anderson28, Chun-Ching Lin35* and Christopher D Richardson28*

Author Affiliations

1 Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

2 Department of Pediatrics and Canadian Center for Vaccinology, IWK Health Centre, Halifax, Nova Scotia, Canada

3 School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan

4 Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

5 Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan

6 Graduate Institute of Pharmaceutical Science and Technology, Central Taiwan University of Science and Technology, Taichung, Taiwan

7 Department of Cosmetic Science, Chia Nan University of Pharmacy and Science, Tainan, Taiwan

8 Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada

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BMC Microbiology 2013, 13:187  doi:10.1186/1471-2180-13-187

Published: 7 August 2013

Abstract

Background

We previously identified two hydrolyzable tannins, chebulagic acid (CHLA) and punicalagin (PUG) that blocked herpes simplex virus type 1 (HSV-1) entry and spread. These compounds inhibited viral glycoprotein interactions with cell surface glycosaminoglycans (GAGs). Based on this property, we evaluated their antiviral efficacy against several different viruses known to employ GAGs for host cell entry.

Results

Extensive analysis of the tannins’ mechanism of action was performed on a panel of viruses during the attachment and entry steps of infection. Virus-specific binding assays and the analysis of viral spread during treatment with these compounds were also conducted. CHLA and PUG were effective in abrogating infection by human cytomegalovirus (HCMV), hepatitis C virus (HCV), dengue virus (DENV), measles virus (MV), and respiratory syncytial virus (RSV), at μM concentrations and in dose-dependent manners without significant cytotoxicity. Moreover, the natural compounds inhibited viral attachment, penetration, and spread, to different degrees for each virus. Specifically, the tannins blocked all these steps of infection for HCMV, HCV, and MV, but had little effect on the post-fusion spread of DENV and RSV, which could suggest intriguing differences in the roles of GAG-interactions for these viruses.

Conclusions

CHLA and PUG may be of value as broad-spectrum antivirals for limiting emerging/recurring viruses known to engage host cell GAGs for entry. Further studies testing the efficacy of these tannins in vivo against certain viruses are justified.

Keywords:
Chebulagic acid; Punicalagin; Tannin; Broad-spectrum antivirals; Viral entry; Glycosaminoglycans