Effect of isoprinosine on rotavirus replication in vitro

Isoprinosine (IPS) is a synthetic drug whose antiviral effect on rotavirus replication in vitro has been characterized in terms of the decrease in metachromasia after acridine orange staining. The present study describes the effect of IPS on the synthesis of viral RNA in vitro. MA-104 cell cultures infected with simian rotavirus strain SA-11 were incubated with zero, 250, 500 and 1,000 microg/ml IPS and 22, 24, 48, 52, 72 and 76 h after infection the cultures were submitted to a 1-h starvation period, followed by a 2-h pulse with 10 microCi/ml of [3H]-uridine. The homogenates of virus-infected cultures treated or not with IPS were submitted to phenol/chloroform extraction followed by polyacrylamide gel electrophoresis. The amount of radioactivity in viral RNA eluted from the gel strips was determined. Inhibition of viral RNA synthesis was highest at the IPS concentration of 1,000 microg/ml at 72 h after infection, corresponding to 78 percent inhibition. Although the results obtained in vitro suggest that IPS may be useful for the treatment of rotavirus infection, an in vivo demonstration of its efficacy is needed.

The in vitro antiviral activity of isoprinosine on simian rotavirus (SA-11)

The antiviral effect of isoprinosine on simian rotavirus (SA-11) replication was studied using MA-104 cell cultures from Rhesus monkey fetal kidney. Isoprinosine (N,N-dimethylamino-2-propanol-p-acetamidobenzoate in association with inosine) added after viral infection (therapeutic test) inhibited viral replication by more than 90%. In these experiments, the drug was added to the medium and replaced daily at concentrations varying from 62.5 microng/ml to l mg/ml. Viral inhibition activity was dependent on drug concentration. No antiviral effect was observed when isoprinosine was tested without replacement (200-500 microng/ml). When isoprinosine (l mg/ml) was added to cell cultures only before viral infection (prophylactic test), inhibition of viral replication occurred but was less than 90%. Inhibition by less than 90% is not considered to be significant in this type of test. Isoprinosine inhibited synthesis of both viral antigen (protein) and viral double-stranded nucleic acid, as monitored by immunofluorescence and acridine orange staining, respectively. Inhibiton of synthesis of viral macromolecules increased with drug concentration

Effect of inosiplex on the humoral and cell-mediated immune responses to intradermal human diploid cell rabies vaccine.

Antigen-stimulated lymphocyte transformation was studied in recipients of intradermal human diploid cell rabies vaccine (HDCV). HDCV was administered intradermally at 8 different anatomical sites, 0.1 ml each, on day 0; followed by another 4-site injection on day 7. Rabies antigen-stimulated in vitro proliferative response was evident as early as 7 days after starting immunization. It reached a peak on day 14 and had declined by day 28. The cellular proliferative response preceded and roughly correlated with the antirabies antibody response. Simultaneous administration of inosiplex, an antiviral and immunopotentiating drug, during the first 10 days of intradermal HDCV immunization did not result in heightened antibody titres or cell-mediated immune response to the vaccine. The number of T cells and the lymphocyte proliferative response to phytohaemagglutinin in inosiplex-treated vaccinees were similarly not significantly different from untreated controls. Our results confirm other previous findings that a specific cell-mediated immune response can be consistently and rapidly induced by an intradermal regimen of HDCV immunization. The addition of inosiplex to this regimen did not enhance the humoral or cell-mediated immune responses to the vaccine. The apparent lack of immunostimulating effect of inosiplex in this setting may be the result of several factors such as the immunization schedule and the immunologic parameters examined.