Therapeutic Strategy for Survival of Mice Infected with Influenza Virus by Combination of S-Adenosyl-L-Methionine and Oseltamivir

Influenza is a highly contagious viral infection of the respiratory system. Many studies provide compelling evidence that the abnormal production of reactive oxygen species is a crucial mediator of acute lung injury in influenza A virus infection. Therefore, antioxidants are potentially useful against this ongoing clinical problem. Our studies showed that S-adenosyl-L-methionine (SAM) has a protective effect in a model of influenza infection in mice. This substance converts into glutathione - the main antioxidant in the body, through a multistep biochemical cycle. In the present study, we report the effect of combined treatment with SAM and the antiviral agent oseltamivir in infected with influenza A virus mice. SAM was given as a single daily dose of 50 and 100 mg/kg in different mice groups, starting from 5 days before infection until day 4 after infection. Oseltamivir was given in a dose of 2.5 mg/kg daily in two intakes for 5 days, starting from 4 h before infection. End-point evaluation was 14 - day survival. Survival was 70% in the treatment with oseltamivir and rose to 90% in the treatment with oseltamivir and SAM in both doses. SAM alone did not show any antiviral activity. The present findings suggest that therapy with molecules converted into antioxidants in the body increases survival by modulating the host defense mechanisms and by a direct antioxidant effect against oxidative stress associated with viral infections. This study demonstrated the effectiveness of combining agents that act through different mechanisms - antiviral drug oseltamivir as a specific neuraminidase inhibitor of influenza virus, and SAM as a precursor of the most important antioxidant - glutathione.