Inhibition of viral DNA polymerases by substrate analogs

Because DNA polymerases play central roles in DNA replication, inhibition of viral DNA polymerases should slow down or stop viral infections. Most of the approved antiviral inhibitors are nucleoside analogs. They are chain terminators like AZT lacking the 3'-hydroxyl group, or are acyclic without a deoxyribose like acyclovir. These drugs are reviewed in detail in Chapter 11 in this book. Because pyrophosphate is a product formed during nucle-


Figure 6.6 Chemical structure of phosphonoformic acid (Foscarnet).

otide incorporation, its analog could bind to and inhibit DNA polymerases. Phosphonoformic acid or Foscarnet (Figure 6.6), a pyrophosphate analog, is an antiherpes drug that binds to the site normally occupied by pyrophosphate and inhibits the catalytic cycle of a herpes DNA polymerase.117

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