ANTIVIRAL ACTIVITY OF Ge-132 (AN ORGANIC GERMANIUM COMPOUND) IN MICE INFECTED WITH INFLUENZA A₂ (H₂N₂) VIRUS

Abstract

Ge-132 [Carboxyethylgermanium sesquioxide; O₃ (GeCH₂CH₂COOH) ₂], an organogermanium compound, has been shown to have antitumor activities in mice and rats, as revealed by inhibition of tumor growth in and prolongation of survival period of these animals. It has also been proved to have, in both human and mice, immunopotentiating activities, through both the induction of interferon-γ in serum and the augmentation of natural killer (NK) cell activity. On the basis of these observations, we study in this paper the effects of Ge-132 on influenza virus infection in mice. When DDI mice were infected with 10 LD₅₀ of influenza A₂ (H₂N₂) virus by inhalation, administration of 20mg/kg or 100mg/kg of Ge-132 for 6 consecutive days starting on the day of infection was found to have a significant protective effect. An increase in the survival fraction, a prolongation of the mean length of survival, an inhibition of the development of lung consolidation, and a decrease in virus titers in the lungs were found in treated groups as compared to control which was given PBS. NK activity in the spleens and lungs of the virus-infected mice was also significantly augmented by orally given Ge-132. In addition, NK cells whose activity was augmented by Ge-132 in vivo revealed a definite killing activity towards NK-insensitive Meth-A cells when the latter were sensitized with influenza virus in vitro. Nevertheless, no direct virocidal or virostatic activities of Ge-132 on the influenza virus were ever found in vitro.
These results indicate that the protective effect of Ge-132 against influenza virus infection in mice seems to be explained by its IFN-γ inducing activity and in particular through its augmentation of NK cells.