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Stages of Virus Replication and Possible Targets of Action of Antiviral Agents

Stage of Replication Classes of Selective Inhibitors

Cell entry Attachment Penetration Uncoating

Release of viral genome Transcription of viral genome*

Transcription of viral messenger RNA Replication of viral genome Translation of viral proteins Regulatory proteins (early) Structural proteins (late) Posttranslational modifications Proteolytic cleavage Myristoylation, glycosylation Assembly of virion components Release

Budding, cell lysis

Soluble receptor decoys, antireceptor antibodies, fusion protein inhibitors Ion channel blockers, capsid stabilizers

Inhibitors of viral DNA polymerase, RNA polymerase, reverse transcriptase, helicase, primase, or integrase

Interferons, antisense oligonucleotides, ribozymes Inhibitors of regulatory proteins

Interferons, assembly protein inhibitors Neuraminidase inhibitors, antiviral antibodies, cytotoxic lymphocytes

Protease inhibitors

*Depends on specific replication strategy of virus, but virus-specified enzyme required for part of process.

Acyclovir is the prototype of antiviral agents that are phosphorylated intracellularly by a viral kinase and subsequently by host cell enzymes to become inhibitors of viral DNA synthesis (Figure 49-2). Related agents include penciclovir and ganciclovir.

Acyclovir and Valacyclovir

CHEMISTRY AND ANTIVIRAL ACTIVITY Acyclovir is an acyclic guanine nucleoside analog that lacks a 3'-hydroxyl on the side chain. Valacyclovir is the l-valyl ester prodrug of acyclovir.

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