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GENERAL CONSIDERATIONS

Viruses are composed of either DNA or RNA, a protein coat (capsid), and, in many, a lipid or lipoprotein envelope. The nucleic acid codes for enzymes involved in replication and for several structural proteins. Viruses use molecules (eg, amino acids, purines, pyrimidines) supplied by the cell and cellular structures (eg, ribosomes) for synthetic functions. Thus, one of the challenges in the development of antiviral agents is identification of the steps in viral replication that are unique to the virus and not used by the normal cell. Among the unique viral events are attachment, penetration, uncoating, RNA-directed DNA synthesis (reverse transcription) or RNA-directed RNA synthesis (RNA viruses), and assembly and release of the intact virion. Each of these steps may have complex elements with the potential for inhibition. For example, assembly of some virus particles requires a unique viral enzyme, protease, and this has led to the development of protease inhibitors (PIs). A general scheme for the points of action of antiviral agents is shown in Figure 8–1.

FIGURE 8–1.

General scheme of antiviral action. The general sequence of viral replication, as in Figure 6–8, is shown with the points of action of selected antiviral agent.

Events in the cell unique to viral replication are the targets for antiviral therapy

In some cases, antiviral agents do not selectively inhibit a unique replicative event but inhibit viral polymerases. Inhibitors of these enzymes take advantage of the fact that the virus is synthesizing nucleic acids more rapidly than the cell; therefore, there is relatively greater inhibition of viral than cellular nucleic acids.

In many acute viral infections, especially respiratory ones, the bulk of viral replication has already occurred when symptoms are beginning to appear. Initiating antiviral therapy at this stage is unlikely to make a major impact on the illness. For these viruses, immuno- or chemoprophylaxis, rather than therapy, is a more logical approach. However, other viral infections are characterized by ongoing viral replication and do benefit from viral inhibition, such as human immunodeficiency virus (HIV) infection and chronic hepatitis B and C.

The principal antiviral agents in current use are discussed according to their modes of action. The first section deals with agents used for most of the non-HIV viruses; the later section reviews the therapeutic agents used for HIV and hepatitis infection. Their features are summarized in Table 8–1.

TABLE 8–1Summary of Antiviral Agents

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