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Viral methyltransferase enzymes catalyze methyl group transfer from S-adenosylmethionine (SAM) to guanine-N7 and ribose-2'-O positions of the viral RNA cap structure, facilitating mRNA stability, translation, and evasion of the host immune response. These enzymes are structurally related across multiple virus families, typically exhibiting a conserved KDKE catalytic tetrad and SAM-binding fold. They are essential for viral replication and pathogenesis, making them attractive candidates for antiviral drug development. Inhibition of viral methyltransferases leads to defective RNA capping and increased detection by host innate immune sensors, attenuating viral propagation and disease.
Competitive inhibition at SAM-binding site Allosteric inhibition of active site Disruption of RNA substrate binding
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