ASPET Otto Krayer award lecture. Molecular targets for antiviral agents. J Pharmacol Exp Ther 2001;297:1–10

There are a number of virus-specific processes within the virus replicative cycle or virus-infected cell that have proven to be attractive targets for chemotherapeutic intervention, i.e., virus adsorption and entry into the cells, reverse (RNA 3 DNA) transcription, viral DNA polymerization, and cellular enzymatic reactions that are associated with viral DNA and RNA synthesis and viral mRNA maturation (i.e., methylation). A variety of che-motherapeutic agents, both nucleoside (and nucleotide) and non-nucleoside entities, have been identified that specifically interact with these viral targets, that selectively inhibit virus replication, and that are either used or considered for clinical use in the treatment of virus infections in humans. Their indi-cations encompass virtually all major human viral pathogens, including human immunodeficiency virus (HIV), hepatitis B virus (HBV), herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), human papilloma virus (HPV), ortho-myxoviruses (influenza A and B), paramyxoviruses [e.g., respi-ratory syncytial virus (RSV)] and hemorrhagic fever viruses (such as Ebola virus). For many years virus diseases have been considered as intractable to selective antiviral chemotherapy because the replicative cycle of the virus was assumed to be too closely interwoven with normal cell metabolism so that any attempt to suppress virus reproduction would be doomed to kill (or severely harm) the uninfected cell as well. With the elucida-tion of virus-specific events as targets for chemotherapeutic attack and the advent of a number of specific antiviral agents, it has become increasingly clear that a selective che-motherapy of virus infections can be achieved and that virus reproduction can be suppressed without deleterious effects on the host. There are currently 30 antiviral drugs that have been offi-cially approved for the treatment of virus infections (De Clercq