NEW DEVELOPMENTS IN ANTIVIRAL CHEMOTHERAP Y

Actually, nucleoside analogues (Aciclovir, Ganciclovir, AZT, DDC) are widely used for the antiviral chemotherapy of herpes and HIV infection . For the treatment of HIV infection, numerous new classes of antivira l compounds (TIBO derivates, proteinase inhibitors) are under developm ent or in the first stages of clinical evaluation. A critical point of antiviral therapy is the emergence of resistant virus mutants under t reatment. Antiviral resistance impairs the long-term efficiency of ant iretroviral therapy in HIV-infected patients. The combination of two o r more compounds which are active against the same (convergent therapy ) or different (divergent therapy) viral targets may delay the emergen ce of antiviral resistance. In vitro experiments showed that nucleosid e analogues induce cellular resistance mechanisms which may be respons ible for an increased release or inactivation of the antiviral compoun d. Recent advances in molecular biology and replication cycle of patho genic viruses have permitted the development of new classes of compoun ds which selectively inactivate one or more critical functions of viru ses (<<drug design>>). Attempts have been made to perform intracellula r immunization (genetic insertion) and genetic therapy. Anti-sense nuc leotides and ribozymes, autocatalytic short fragments, which inhibit v irus replication by interfering with transcription or translation are under evaluation. However, in the view of numerous unsolved problems, therapeutic use in humans is not to be expected in the next years.