Antiviral effects of rhamnan sulfate

Effect of rhamnan sulfate on the suppression of viral proliferation in cultured cells

Background and aims

Rhamnan sulfate is known to have an antiviral effect with respect to the AIDS virus, the herpes virus, and the cytomegalovirus (Lee JB, Hayashi K, Hayashi T, Sankawa U, Maeda M, Planta Med. 1999 65, pp. 439-41). Structurally, viruses can be divided into those that possess and those that do not possess envelopes. These envelopes consist of lipids and proteins, and when viruses are released from the host cells, they are equipped with the membranes of the host cells. In order to clarify the types of virus on which the antiviral properties of rhamnan sulfate are effective, we assessed its effect on 12 different types of viruses.

 

Study method

We prepared virus solutions and infected the cultured cells that would host the viruses, under the following conditions:

• A) The virus solution together with rhamnan sulfate was added to the cells. After 1 hour, the virus solution was washed away and rhamnan sulfate was added again.
• B) Infection with the virus was carried out for 1 hour, and after washing, rhamnan sulfate was added to the cells.

After culturing for 24 hours, to investigate the number of viruses that had propagated after the host cells had been infected, we disrupted the cell membrane of the host cells and assessed the number of viruses using the plaque assay (a method for measuring number of viruses). Various concentrations of rhamnan sulfate were added, and we sought the half-maximal viral proliferation-inhibitory concentration (IC₅₀). The lower the IC₅₀, the greater is the strength of inhibitory activity. In the case of method A, rhamnan sulfate was present from the moment when the virus adsorbed and invaded the cells; whereas in the case of method B, it was added after viral adsorption in the cells.

 

Results

Rhamnan sulfate possesses a strong viral proliferation-inhibitory effect against viruses with envelopes, but it became clear that there is almost no antiviral effect against viruses without envelopes. Regardless of the type of envelope possessed by a virus, method A, in which rhamnan sulfate was added at the same time as the infection with the virus, resulted in a stronger inhibitory effect.

 

Conclusion

Rhamnan sulfate is more effective when added at the same time as the infection rather than when added later, and it seems to be particularly effective at the initial stage of host-cell infection. These results suggested that it is effective in inhibiting infection owing to its ability to block adsorption of the virus on cell membranes.

 

Effects of rhamnan sulfate on influenza virus proliferation-prevention and immunostimulation in mice

Background and aim

In order to clarify the antiviral effects of rhamnan sulfate identified on the basis of studies in cultured cells, we investigated the quantity of virus and the antibody titer upon oral administration of rhamnan sulfate in mice infected with the influenza A virus. Our aim was to determine how effective rhamnan sulfate is, in vivo.

 

Study method

After infection with the influenza A virus, 5 mg of rhamnan sulfate was administered to mice orally, twice a day. For the purpose of comparison, we administered only water or the anti-influenza drug Tamiflu. The blood and lung samples were collected 3 days and 7 days after infection with the virus, and blood was also collected on the fourteenth day after infection.

 

Results

Amount of influenza virus in the lungs

Rhamnan sulfate was administered to the mice infected with the influenza virus, and we discovered a significant decrease in the amount of virus in their lungs, in comparison with the mice to which only water had been administered.

 

Amount of influenza A-type antibodies in the blood

Influenza antibodies in the blood of mice that were administered rhamnan sulfate showed a tendency to increase in quantity 7 days after infection, in contrast to the mice that were administered only water. On the fourteenth day after infection, it became clear that there had been a further increase in antibodies in the group that was administered rhamnan sulfate, in comparison with the group that was administered only water.

 

 

Conclusion

Due to its immunostimulatory effect, rhamnan sulfate generates a large quantity of antibodies against the influenza A virus. The increase of antibodies may be considered effective in reducing the virus proliferation.