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Iota-Carrageenan is a potent inhibitor of rhinovirus infection.

Grassauer A, Weinmuellner R, Meier C, Pretsch A, Prieschl-Grassauer E, Unger H - Virol. J. (2008)

Bottom Line: Despite significant efforts, no anti-viral agent is approved for the prevention or treatment of HRV-infection.In addition, Iota-Carrageenan effectively prevents the replication of HRV1A, HRV2, HRV8, HRV14, HRV16, HRV83 and HRV84 in primary human nasal epithelial cells in culture.Since HRV infections predominately occur in the nasal cavity and the upper respiratory tract, a targeted treatment with a product containing Iota-Carrageenan is conceivable.

View Article: PubMed Central - HTML - PubMed

Affiliation: Marinomed Biotechnologie GmbH, Veterinaerplatz 1/HA, A-1210 Vienna, Austria. andreas.grassauer@marinomed.com

ABSTRACT

Background: Human rhinoviruses (HRVs) are the predominant cause of common cold. In addition, HRVs are implicated in the worsening of COPD and asthma, as well as the loss of lung transplants. Despite significant efforts, no anti-viral agent is approved for the prevention or treatment of HRV-infection.

Results: In this study we demonstrate that Iota-Carrageenan, a sulphated polysaccharide derived from red seaweed, is a potent anti-rhinoviral substance in-vitro. Iota-Carrageenan reduces HRV growth and inhibits the virus induced cythopathic effect of infected HeLa cells. In addition, Iota-Carrageenan effectively prevents the replication of HRV1A, HRV2, HRV8, HRV14, HRV16, HRV83 and HRV84 in primary human nasal epithelial cells in culture. The data suggest that Iota-Carrageenan acts primarily by preventing the binding or the entry of virions into the cells.

Conclusion: Since HRV infections predominately occur in the nasal cavity and the upper respiratory tract, a targeted treatment with a product containing Iota-Carrageenan is conceivable. Clinical trials are needed to determine whether Iota-Carrageenan-based products are effective in the treatment or prophylaxis of HRV infections.

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Effect of Iota carageenan on the replication of HRVstrains 1A, 2, 8, 14, 16, 39, 83 and 84 on human nasal epithelial cells. HNep cells were grown in 96-well plates were infected with different HRV strains (indicated at the top of each panel; 0,1 TCID50/cell) in the presence of Iota-Carrageenan at the concentrations indicated at the x-axis. 30 minutes after infection the inoculum was removed and medium containing Iota-Carrageenan with the same concentration was added. Viral titers in the supernatants of infected cells were determined after 48 h by TCID50 assay on HeLa cells (y-axis). Bars represent means from four parallel experiments, standard deviations are indicated.
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Figure 6: Effect of Iota carageenan on the replication of HRVstrains 1A, 2, 8, 14, 16, 39, 83 and 84 on human nasal epithelial cells. HNep cells were grown in 96-well plates were infected with different HRV strains (indicated at the top of each panel; 0,1 TCID50/cell) in the presence of Iota-Carrageenan at the concentrations indicated at the x-axis. 30 minutes after infection the inoculum was removed and medium containing Iota-Carrageenan with the same concentration was added. Viral titers in the supernatants of infected cells were determined after 48 h by TCID50 assay on HeLa cells (y-axis). Bars represent means from four parallel experiments, standard deviations are indicated.

Mentions: Since more than 100 distinctive HRV serotypes are circulating in humans it was important to reveal whether Iota-Carrageenan is also effective against other strains of HRVs. The work of Ledford et al. shows that the EC50 concentration against HRV of the capsid binder Pleconaril has a strain dependent variability between 0,01 μg/ml and >12,5 μg/ml [17]. Based on this work we selected HRV1A, HRV16 and HRV8 for testing. These three viruses belong to the HRV-A virus group and are in contrast to HRV2 relatively insensitive to Pleconaril. From the HRV-B virus group we tested the Pleconaril sensitive strain HRV83, the moderate sensitive strain HRV14, and HRV84, a strain that cannot be inhibited by Pleconaril at a concentration of 12,5 μg/ml. Primary human nasal epithelial cells were seeded in 96-well plates (4.8 * 103 cells per well) and infected with HRV an amount of input virus of 2 TCID50/cell. Supernatants were harvested between 48–72 hours after infection and the viral titers were determined by TCID50 assays on HeLa cells. While HRV1, HRV14, HRV16 and HRV83 replicated to titers above 107 TCID50/ml, HRV8 reached a titer of 105,1 TCID50/ml and HRV84 a titer of 104,1 TCID50/ml (Figure 6). A Iota-Carrageenan concentration of 50 μg/ml was sufficient to reduce the replication on HNep cells of all tested viruses by more than 3 orders of magnitude (99,9%). At a Iota-Carrageenan concentration of 5 μg/ml an inhibition of greater than 99% was observed for HRV1, HRV14, HRV16, HRV83 and HRV84. However, for HRV8 a reduction from 105,2 TCID50/ml to 103,8 TCID50/ml was observed at 5 g/ml Iota-Carrageenan. No toxic effects have been observed on HNep cells at the highest tested Iota-Carrageenan concentration of 500 μg/ml. This result demonstrates that Iota-Carrageenan can effectively block the replication of six distinct HRV strain on HNEp cells.


Iota-Carrageenan is a potent inhibitor of rhinovirus infection.

Grassauer A, Weinmuellner R, Meier C, Pretsch A, Prieschl-Grassauer E, Unger H - Virol. J. (2008)

Effect of Iota carageenan on the replication of HRVstrains 1A, 2, 8, 14, 16, 39, 83 and 84 on human nasal epithelial cells. HNep cells were grown in 96-well plates were infected with different HRV strains (indicated at the top of each panel; 0,1 TCID50/cell) in the presence of Iota-Carrageenan at the concentrations indicated at the x-axis. 30 minutes after infection the inoculum was removed and medium containing Iota-Carrageenan with the same concentration was added. Viral titers in the supernatants of infected cells were determined after 48 h by TCID50 assay on HeLa cells (y-axis). Bars represent means from four parallel experiments, standard deviations are indicated.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2562995&req=5

Figure 6: Effect of Iota carageenan on the replication of HRVstrains 1A, 2, 8, 14, 16, 39, 83 and 84 on human nasal epithelial cells. HNep cells were grown in 96-well plates were infected with different HRV strains (indicated at the top of each panel; 0,1 TCID50/cell) in the presence of Iota-Carrageenan at the concentrations indicated at the x-axis. 30 minutes after infection the inoculum was removed and medium containing Iota-Carrageenan with the same concentration was added. Viral titers in the supernatants of infected cells were determined after 48 h by TCID50 assay on HeLa cells (y-axis). Bars represent means from four parallel experiments, standard deviations are indicated.
Mentions: Since more than 100 distinctive HRV serotypes are circulating in humans it was important to reveal whether Iota-Carrageenan is also effective against other strains of HRVs. The work of Ledford et al. shows that the EC50 concentration against HRV of the capsid binder Pleconaril has a strain dependent variability between 0,01 μg/ml and >12,5 μg/ml [17]. Based on this work we selected HRV1A, HRV16 and HRV8 for testing. These three viruses belong to the HRV-A virus group and are in contrast to HRV2 relatively insensitive to Pleconaril. From the HRV-B virus group we tested the Pleconaril sensitive strain HRV83, the moderate sensitive strain HRV14, and HRV84, a strain that cannot be inhibited by Pleconaril at a concentration of 12,5 μg/ml. Primary human nasal epithelial cells were seeded in 96-well plates (4.8 * 103 cells per well) and infected with HRV an amount of input virus of 2 TCID50/cell. Supernatants were harvested between 48–72 hours after infection and the viral titers were determined by TCID50 assays on HeLa cells. While HRV1, HRV14, HRV16 and HRV83 replicated to titers above 107 TCID50/ml, HRV8 reached a titer of 105,1 TCID50/ml and HRV84 a titer of 104,1 TCID50/ml (Figure 6). A Iota-Carrageenan concentration of 50 μg/ml was sufficient to reduce the replication on HNep cells of all tested viruses by more than 3 orders of magnitude (99,9%). At a Iota-Carrageenan concentration of 5 μg/ml an inhibition of greater than 99% was observed for HRV1, HRV14, HRV16, HRV83 and HRV84. However, for HRV8 a reduction from 105,2 TCID50/ml to 103,8 TCID50/ml was observed at 5 g/ml Iota-Carrageenan. No toxic effects have been observed on HNep cells at the highest tested Iota-Carrageenan concentration of 500 μg/ml. This result demonstrates that Iota-Carrageenan can effectively block the replication of six distinct HRV strain on HNEp cells.

Bottom Line: Despite significant efforts, no anti-viral agent is approved for the prevention or treatment of HRV-infection.In addition, Iota-Carrageenan effectively prevents the replication of HRV1A, HRV2, HRV8, HRV14, HRV16, HRV83 and HRV84 in primary human nasal epithelial cells in culture.Since HRV infections predominately occur in the nasal cavity and the upper respiratory tract, a targeted treatment with a product containing Iota-Carrageenan is conceivable.

View Article: PubMed Central - HTML - PubMed

Affiliation: Marinomed Biotechnologie GmbH, Veterinaerplatz 1/HA, A-1210 Vienna, Austria. andreas.grassauer@marinomed.com

ABSTRACT

Background: Human rhinoviruses (HRVs) are the predominant cause of common cold. In addition, HRVs are implicated in the worsening of COPD and asthma, as well as the loss of lung transplants. Despite significant efforts, no anti-viral agent is approved for the prevention or treatment of HRV-infection.

Results: In this study we demonstrate that Iota-Carrageenan, a sulphated polysaccharide derived from red seaweed, is a potent anti-rhinoviral substance in-vitro. Iota-Carrageenan reduces HRV growth and inhibits the virus induced cythopathic effect of infected HeLa cells. In addition, Iota-Carrageenan effectively prevents the replication of HRV1A, HRV2, HRV8, HRV14, HRV16, HRV83 and HRV84 in primary human nasal epithelial cells in culture. The data suggest that Iota-Carrageenan acts primarily by preventing the binding or the entry of virions into the cells.

Conclusion: Since HRV infections predominately occur in the nasal cavity and the upper respiratory tract, a targeted treatment with a product containing Iota-Carrageenan is conceivable. Clinical trials are needed to determine whether Iota-Carrageenan-based products are effective in the treatment or prophylaxis of HRV infections.

Show MeSH
Related in: MedlinePlus