We live in a time of rapid development of antiviral compounds. For selective chemotherapy of viral infections, a drug should inhibit virus replication when used at concentrations not detrimental to the host. A number of antiviral drugs have been formally licensed and are widely used for the chemotherapy of specific viral infections. Other antiviral agents are being developed. These fall primarily in three classes:
The mechanisms of action targeting virus-specific events are being studied. Antiviral chemotherapy offers a decisive approach to the control of virus, notwithstanding some current limitations.
Specificity against virus replication is the key issue in chemotherapy. Because of the close interaction between virus replication and normal cellular metabolism, it was originally thought too difficult to interrupt the virus replicative cycle without adversely affecting the host cell metabolism. It is now clear, however, that several events in the virus replicative cycle either do not occur in normal uninfected cells or are controlled by virus-specified enzymes that differ structurally and functionally from the corresponding host cell enzymes.
Quite schematically, the virus replicative cycle can be divided into 10 steps (Fig. 52-1):
Adsorption, penetration, and uncoating are typical examples of replicative events that are specific for virus infection and do not occur in uninfected cells (see Ch. 42). Examples of virus replication steps controlled by virus-specified enzymes are the transcription of positive-sense RNA to DNA (catalyzed by the reverse transcriptase associated with retroviruses), the replication of DNA to DNA (catalyzed by the DNA polymerases of herpesviruses), and the proteolytic cleavage of viral precursor proteins (catalyzed by the protease of human immunodeficiency virus).