Alessandra Fraternale, Maria Filomena Paoletti, Anna Casabianca, Lucia Nencioni, Enrico Garaci, Anna Teresa Palamara, and Mauro Ma

In animal cells, reduced glutathione (GSH) is the most common non-protein thiol. Its de novo and salvage synthesis helps to keep the cellular environment under control. GSH is the most effective intracellular antioxidant, and glutathione-S-transferases (GST) and glutathione peroxidases catalyze the detoxification of a number of electrophilic compounds and peroxides (GPx). As a result, the ratio of reduced to oxidized glutathione serves as a reliable indicator of the cell’s antioxidative ability. A lack of GSH places the cell at risk of oxidative stress. Several studies have shown that GSH and molecules that replenish intracellular GSH levels can be used in antiviral therapy. This chapter discusses GSH and its analogs’ non-traditional position as antiviral drugs.