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

Lin LT, Chen TY, Lin SC, Chung CY, Lin TC, Wang GH, Anderson R, Lin CC, Richardson CD - BMC Microbiol. (2013)

Bottom Line: These compounds inhibited viral glycoprotein interactions with cell surface glycosaminoglycans (GAGs).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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

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.

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Related in: MedlinePlus

Structures of chebulagic acid (CHLA) and punicalagin (PUG). The chemical structures of the two hydrolyzable tannins under study, chebulagic acid (CHLA) and punicalagin (PUG), are presented.
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Figure 1: Structures of chebulagic acid (CHLA) and punicalagin (PUG). The chemical structures of the two hydrolyzable tannins under study, chebulagic acid (CHLA) and punicalagin (PUG), are presented.

Mentions: In our previous study, we identified chebulagic acid (CHLA) and punicalagin (PUG) (Figure 1), two hydrolyzable tannins isolated from Terminalia chebula Retz., (T. chebula) as inhibitors of HSV type 1 (HSV-1) entry and spread [33]. We demonstrated that the two structurally-related compounds mediated their antiviral activities by targeting HSV-1 viral glycoproteins that interact with cell surface GAGs. Taking note of the fact that many viruses employ GAGs to initially bind to the host cell, and based on evidence that CHLA and PUG may act as GAG-competitors, we explored the antiviral-potential of these two tannins against a number of viruses known to interact with GAGs. Viral models included DENV, HCMV, HCV, MV, and RSV (Table 1). Many of the diseases associated with these viruses lack preventative vaccines and/or drug treatment options [1-4,13,34-36]. Indeed, both CHLA and PUG efficiently inhibited entry and spread of these viruses to varying degrees. We suggest that CHLA and PUG have potential as novel cost-effective and broad-spectrum antivirals for controlling emerging/recurring infections by viruses that engage host cell surface GAGs.


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

Lin LT, Chen TY, Lin SC, Chung CY, Lin TC, Wang GH, Anderson R, Lin CC, Richardson CD - BMC Microbiol. (2013)

Structures of chebulagic acid (CHLA) and punicalagin (PUG). The chemical structures of the two hydrolyzable tannins under study, chebulagic acid (CHLA) and punicalagin (PUG), are presented.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750913&req=5

Figure 1: Structures of chebulagic acid (CHLA) and punicalagin (PUG). The chemical structures of the two hydrolyzable tannins under study, chebulagic acid (CHLA) and punicalagin (PUG), are presented.
Mentions: In our previous study, we identified chebulagic acid (CHLA) and punicalagin (PUG) (Figure 1), two hydrolyzable tannins isolated from Terminalia chebula Retz., (T. chebula) as inhibitors of HSV type 1 (HSV-1) entry and spread [33]. We demonstrated that the two structurally-related compounds mediated their antiviral activities by targeting HSV-1 viral glycoproteins that interact with cell surface GAGs. Taking note of the fact that many viruses employ GAGs to initially bind to the host cell, and based on evidence that CHLA and PUG may act as GAG-competitors, we explored the antiviral-potential of these two tannins against a number of viruses known to interact with GAGs. Viral models included DENV, HCMV, HCV, MV, and RSV (Table 1). Many of the diseases associated with these viruses lack preventative vaccines and/or drug treatment options [1-4,13,34-36]. Indeed, both CHLA and PUG efficiently inhibited entry and spread of these viruses to varying degrees. We suggest that CHLA and PUG have potential as novel cost-effective and broad-spectrum antivirals for controlling emerging/recurring infections by viruses that engage host cell surface GAGs.

Bottom Line: These compounds inhibited viral glycoprotein interactions with cell surface glycosaminoglycans (GAGs).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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

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.

Show MeSH
Related in: MedlinePlus