Crystal structure analysis of Flavivirus methyltransferases uncovered a flavivirus-conserved
cavity located next to the binding site for its cofactor, S-adenosyl-methionine (SAM).
Chemical derivatization of S-adenosyl-homocysteine (SAH), the product inhibitor of the
methylation reaction, with substituents that extend into the identified cavity, generated
inhibitors that showed improved and selective activity against dengue virus
methyltransferase (MTase), but not related human enzymes. Crystal structure of dengue …