Inhibition of human and avian type A Influenza virus multiplication performed by MESNA

The antiviral activity of MESNA, a thiol group compound, was evaluated in LLC-MK2 cells infected by Influenza virus. MESNA was able to inhibit viral multiplicaton in a dose-dependent fashion and virus yield, obtained both with HA and plaque assaies, was reduced at concentrations which did not suppress protein synthesis in mock-infected cells. MESNA treatment determined a marked reduction of the normal synthesis of early and late virus-induced proteins suggesting an action on viral transcriptase. However, “in vitro” assay of viral RNA dependent-RNA polymerase activity performed on purified virions showed negative results in that MESNA was not able to inhibit or block virus enzyme activity. This evidence led us to hypothesise a possible involvement of a cellular factor (s). We have investigated the role and the concentration of the ratio Ox-Red glutathione, GSSG / GSH. Results obtained demonstrate a correlation between the intracellular concentration of GSH and progression/ inhibition of viral infection. In particular, the results reported here demonstrate that the amounts of GSH reached into the cells are a direct consequence of MESNA treatments. Data obtained with human influenza virus strain, A, NWS, H1N1, were completely reproducible and comparable with those obtained with avian influenza virus strain, A, Ulster 73, H7N1. Furthermore, data obtained in MDCK cells were comparable to those, above described, obtained in LLC-MK2 cells. Corresponding Author: prof. Giorgio Conti