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

Liang Tzung Lin, Ting Ying Chen, Song-Chow Lin, Chueh Yao Chung, Ta Chen Lin, Guey Horng Wang, Robert Anderson, Chun Ching Lin, Christopher D. Richardson

Research output: Contribution to journalArticle

57 Citations (Scopus)

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.

Original languageEnglish
Article number187
JournalBMC Microbiology
Volume13
Issue number1
DOIs
Publication statusPublished - 2013

Fingerprint

Glycosaminoglycans
Antiviral Agents
Tannins
Viruses
Virus Attachment
Virus Internalization
Measles virus
Dengue Virus
Respiratory Syncytial Viruses
Cytomegalovirus Infections
Hepacivirus
Hydrolyzable Tannins
Human Herpesvirus 1
Cell Communication
Glycoproteins
punicalagin
chebulagic acid
Infection

Keywords

  • Broad-spectrum antivirals
  • Chebulagic acid
  • Glycosaminoglycans
  • Punicalagin
  • Tannin
  • Viral entry

ASJC Scopus subject areas

  • Microbiology (medical)
  • Microbiology

Cite this

Broad-spectrum antiviral activity of chebulagic acid and punicalagin against viruses that use glycosaminoglycans for entry. / Lin, Liang Tzung; Chen, Ting Ying; Lin, Song-Chow; Chung, Chueh Yao; Lin, Ta Chen; Wang, Guey Horng; Anderson, Robert; Lin, Chun Ching; Richardson, Christopher D.

In: BMC Microbiology, Vol. 13, No. 1, 187, 2013.

Research output: Contribution to journalArticle

Lin, Liang Tzung ; Chen, Ting Ying ; Lin, Song-Chow ; Chung, Chueh Yao ; Lin, Ta Chen ; Wang, Guey Horng ; Anderson, Robert ; Lin, Chun Ching ; Richardson, Christopher D. / Broad-spectrum antiviral activity of chebulagic acid and punicalagin against viruses that use glycosaminoglycans for entry. In: BMC Microbiology. 2013 ; Vol. 13, No. 1.
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AB - 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.

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