Phosphoanalogues of amino acids involved in methionine metabolism as a new source of antiviral compounds

Abstract

84 Biological methylation is of primary importance in cell metabolism [1]. The major donor of methyl groups used in biological methylation is S-adenosylmethionine (Met(Ado)), which is converted to S-adenosylhomocysteine Hcy(Ado), the only inhibitor of methylation reactions. The intracellular level of Met(Ado) is regulated by hydrolase (Fig. 1). The nucleoside inhibitors of this enzyme increase the concentration of S-adenosylhomocysteine, which results in suppression of activity of Met(Ado)-dependent methyltransferases, including viral mRNA methylases, and determines the antiviral activity of such compounds [1, 2]. The selectivity of effect of hydrolase inhibitors is low. These compounds inhibit methylation of the main classes of biological molecules, which determines the toxicity of antiviral compounds belonging to the group of nucleoside inhibitors. The search for specific inhibitors of Met(Ado) exchange and methionine metabolism (Fig. 1) remains to be a promising direction in the chemotherapy of viral infections [2].