Abstract
Replication proteins in large DNA viruses such as herpesviruses or poxviruses have functional analogs in eukaryotes. Their DNA-dependent DNA polymerases are multifunctional enzymes with polymerase and exonuclease activities and are structurally related to replicative eukaryotic polymerases such as human DNA polymerases α, δ, ζ, and ε. These enzymes constitute good targets to develop antiviral drugs. In fact, all antiviral drugs currently used for prevention and treatment of infections caused by herpesviruses act through the inhibition of their DNA polymerases. In this review, we provide a general overview of the biochemical and structural properties of herpesvirus and poxvirus DNA polymerases. Currently available antiherpetic drugs and amino acid substitutions in the DNA polymerase that confer resistance to those inhibitors are discussed for herpes simplex virus, varicella zoster virus, and human cytomegalovirus. Finally, the chapter also presents a brief description of some novel investigational drugs that are under preclinical development or under various phases of clinical trials to act as effective inhibitors of herpesvirus or poxvirus DNA polymerases.
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