The past as prelude to the future: history, status, and future of antiviral drugs.
OBJECTIVE
To review the first generation of antiviral agents (e.g., idoxuridine, amantadine, vidarabine) that paralleled discovery of antineoplastic agents.


METHODS
A MEDLINE search (1962 to 1996) of the English-language literature pertaining to antiviral agents was performed.


METHODS
All articles were considered for this review. Pertinent references on antiviral therapy, as judged by the author, were selected.


RESULTS
Acyclovir, the first second-generation antiviral agent, has a known selective mechanism of action and provides the model for development of future antiviral therapies. Despite the safety and clinical value of acyclovir, therapy does not prevent establishment of latency or decrease frequency of occurrences, resistance has been documented, and outcome is frequently poor. With the emergence of the HIV/AIDS epidemic, several antiretroviral agents have been developed and approved. However, none of the four available nucleoside analogs provides a cure.


CONCLUSIONS
Viral resistance has emerged as an important component of antiviral therapy. Improved therapies for cytomegalovirus are needed. Several new therapies for herpes zoster, including prodrugs, are licensed or in Phase III clinical trials. Future directions include the use of molecular biologic techniques to identify enzymes unique to viral replication and to accelerate diagnosis of viral diseases.
Whitley
R J
RJ
University of Alabama at Birmingham 35233, USA.
D000212:Acyclovir / Q000494:pharmacology / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000266:history / Q000494:pharmacology / Q000627:therapeutic use*; D004341:Drug Evaluation; D005544:Forecasting; D015658:HIV Infections / Q000188:drug therapy; D006566:Herpesviridae Infections / Q000188:drug therapy*; D049673:History, 20th Century; D006801:Humans
D000998:Antiviral Agents; D000212:Acyclovir