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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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Dose response of CHLA and PUG treatments against multiple viruses. Host cells for each virus (HEL for HCMV; Huh-7.5 for HCV; Vero for DENV-2, CHO-SLAM for MV; HEp-2 for RSV, and A549 for VSV and ADV-5) were co-treated with viral inoculum and increasing concentrations of test compounds for 1 – 3 h before being washed, incubated, and analyzed for virus infection by plaque assays, EGFP expression analysis, or luciferase assay as described in Methods. (A) Schematic of the experiment (shown on the left) with the virus concentration (PFU/well or MOI), co-treatment time (i), and the subsequent viral incubation period (ii) indicated for each virus in the table on the right. (B) Antiviral effect of CHLA against multiple viruses. (C) Antiviral effect of PUG against multiple viruses. Results are plotted against values for the DMSO control treatment of virus infections and the data shown are means ± the standard errors of the mean (SEM) from three independent experiments. See text for details.
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Figure 2: Dose response of CHLA and PUG treatments against multiple viruses. Host cells for each virus (HEL for HCMV; Huh-7.5 for HCV; Vero for DENV-2, CHO-SLAM for MV; HEp-2 for RSV, and A549 for VSV and ADV-5) were co-treated with viral inoculum and increasing concentrations of test compounds for 1 – 3 h before being washed, incubated, and analyzed for virus infection by plaque assays, EGFP expression analysis, or luciferase assay as described in Methods. (A) Schematic of the experiment (shown on the left) with the virus concentration (PFU/well or MOI), co-treatment time (i), and the subsequent viral incubation period (ii) indicated for each virus in the table on the right. (B) Antiviral effect of CHLA against multiple viruses. (C) Antiviral effect of PUG against multiple viruses. Results are plotted against values for the DMSO control treatment of virus infections and the data shown are means ± the standard errors of the mean (SEM) from three independent experiments. See text for details.

Mentions: The respective cell lines and relative viral dose used, as well as the incubation periods for test compound treatment and for viral cytopathic effects to take place, are indicated in Table 2 and Figure 2A for each specific virus.


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)

Dose response of CHLA and PUG treatments against multiple viruses. Host cells for each virus (HEL for HCMV; Huh-7.5 for HCV; Vero for DENV-2, CHO-SLAM for MV; HEp-2 for RSV, and A549 for VSV and ADV-5) were co-treated with viral inoculum and increasing concentrations of test compounds for 1 – 3 h before being washed, incubated, and analyzed for virus infection by plaque assays, EGFP expression analysis, or luciferase assay as described in Methods. (A) Schematic of the experiment (shown on the left) with the virus concentration (PFU/well or MOI), co-treatment time (i), and the subsequent viral incubation period (ii) indicated for each virus in the table on the right. (B) Antiviral effect of CHLA against multiple viruses. (C) Antiviral effect of PUG against multiple viruses. Results are plotted against values for the DMSO control treatment of virus infections and the data shown are means ± the standard errors of the mean (SEM) from three independent experiments. See text for details.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Dose response of CHLA and PUG treatments against multiple viruses. Host cells for each virus (HEL for HCMV; Huh-7.5 for HCV; Vero for DENV-2, CHO-SLAM for MV; HEp-2 for RSV, and A549 for VSV and ADV-5) were co-treated with viral inoculum and increasing concentrations of test compounds for 1 – 3 h before being washed, incubated, and analyzed for virus infection by plaque assays, EGFP expression analysis, or luciferase assay as described in Methods. (A) Schematic of the experiment (shown on the left) with the virus concentration (PFU/well or MOI), co-treatment time (i), and the subsequent viral incubation period (ii) indicated for each virus in the table on the right. (B) Antiviral effect of CHLA against multiple viruses. (C) Antiviral effect of PUG against multiple viruses. Results are plotted against values for the DMSO control treatment of virus infections and the data shown are means ± the standard errors of the mean (SEM) from three independent experiments. See text for details.
Mentions: The respective cell lines and relative viral dose used, as well as the incubation periods for test compound treatment and for viral cytopathic effects to take place, are indicated in Table 2 and Figure 2A for each specific virus.

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