Antiviral Therapy

ANTIVIRAL THERAPY

GENERAL CONSIDERATIONS

Viruses are comprised 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), 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 devel-opment of protease inhibitors.

In some cases, antivirals do not selectively inhibit a unique replicative event but in-hibit DNA polymerase. Inhibitors of this enzyme take advantage of the fact that the virus is synthesizing nucleic acids more rapidly than the cell, so there is relatively greater inhi-bition of viral than cellular DNA. 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, many 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. Their features are summarized in Table 13 – 2.