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Efficacy of S26308 against guinea pig cytomegalovirus infection
M Chen1, B P Griffith, H L Lucia
1Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Abstract:
Prophylactic use of antiviral agents against cytomegalovirus (CMV) is particularly indicated for the immunocompromised host because morbidity and mortality due to CMV occur most frequently following immunosuppression. We have evaluated the new Riker compound S26308 for its therapeutic and prophylactic antiviral activity against CMV in guinea pigs. The efficacy of the compound was assessed in vitro in guinea pig embryo cells and in vivo in both immunocompetent and immunocompromised guinea pigs. Guinea pig CMV plaque formation was reduced only in cells treated with S26308 prior to virus infection. The antiviral activity remained even when the compound was removed after virus absorption and was due to neither virus destruction nor inhibition of cell growth. The frequency of viremia was reduced in guinea pigs for which S26308 therapy was initiated 24 h prior to virus inoculation compared with sham-treated animals. This reduction in the frequency of viremia did not prevent virus spread to target tissues but did result in a reduction of the severity of CMV-induced disease in immunocompromised guinea pigs. Low levels of interferon were detected in supernatants of S26308-treated cells, and interferon was detected in the serum of guinea pigs given S26308. These results indicate that S26308 can induce interferon and reduce CMV infectivity in vivo and in vitro when used prophylactically. This antiviral activity, although modest, was accompanied by beneficial effects on CMV-induced morbidity and mortality. Prophylactic use of S26308 in combination with other therapeutic agents may be a useful strategy against CMV infections.
Insights
Prophylactic use of Riker compound S26308 showed modest antiviral activity against cytomegalovirus (CMV) in guinea pigs. This compound reduced CMV infectivity and disease severity, suggesting potential for combination therapy against CMV infections.
Area of Science:
- Virology
- Immunology
- Pharmacology
Background:
- Cytomegalovirus (CMV) poses significant risks to immunocompromised individuals.
- Antiviral prophylaxis is crucial for managing CMV in high-risk populations.
- The need for effective prophylactic agents against CMV remains critical.
Purpose of the Study:
- To evaluate the prophylactic and therapeutic antiviral activity of Riker compound S26308 against CMV.
- To assess the efficacy of S26308 in both in vitro and in vivo guinea pig models.
- To investigate the mechanism of action and clinical benefits of S26308.
Main Methods:
- In vitro assessment of S26308 on CMV plaque formation in guinea pig embryo cells.
- In vivo evaluation in both immunocompetent and immunocompromised guinea pigs.
- Monitoring viremia, virus spread, disease severity, and interferon induction.
Main Results:
- S26308 significantly reduced CMV plaque formation when cells were pre-treated.
- Prophylactic S26308 administration in guinea pigs decreased viremia frequency.
- Reduced viremia correlated with decreased severity of CMV-induced disease in immunocompromised hosts.
Conclusions:
- S26308 exhibits prophylactic antiviral activity against CMV in vitro and in vivo.
- The compound appears to induce interferon, contributing to its antiviral effects.
- Prophylactic S26308, potentially in combination therapy, shows promise for managing CMV infections.