Chemotherapy

Inhibitors of certain steps in viral replication can be used as chemo­therapeutic agents to treat viral infections. In practical terms, it is much more important to inhibit the synthesis of viral nucleic acid than of viral proteins. The main obstacles involved are the low level of specificity of the agents in some cases (toxic effects because cellular metabolism is also affected) and the necessity of commencing therapy very early in the infection cycle.

Problems of chemotherapy. As described on viral replication is com­pletely integrated in cell metabolism. The virus supplies only the genetic information for proteins to be synthesized by the cell. This close association between viruses and their host cells is a source of some essential difficulties encountered when developing virus-specific chemotherapeutics, since any interference with viral synthesis is likely to affect physiological cellular syn­thetic functions as well. Specific intervention is only possible with viruses that code for their own enzymes (e.g., polymerases or proteases), which en­zymes also react with viral substrates. Another problematic aspect is the ne­cessity of administering chemotherapeutics (Table 1) early, preferably be­fore clinical symptoms manifest, since the peak of viral replication is then usually already past.

Table 1 The Most Important Antiviral Chemotherapeutics

Development of resistance to chemotherapeutics. Acyclovir-resistant strains of herpesviruses, in particular herpes simplex viruses, are occasionally isolated. Less frequently, cytomegaly viruses resistant to ganciclovir are also found. These viruses possess a thymidine kinase or DNA polymerase altered by mutation. Infections caused by resistant herpesviruses are also observed in immunodeficient patients; the pathogens no longer respond to therapy after long-term treatment of dermal or mucosal efflorescences.

There are, as yet, no standardized resistance tests for chemotherapy-re­sistant viruses, so that the usefulness of such test results is of questionable value in confirmed cases. Also, the results obtained in vitro unfortunately do not correlate well with the cases of resistant viruses observed in clinical set­tings.

References

Fritz H. Kayser, M.D. Emeritus Professor of Medical Microbiology Institute of Medical Microbiology, University of Zurich, Zurich, SwitzerlandThieme 2005, Stuttgart ! New York.