Antivirals other than for HIV therapy

This review concentrates on drugs directed at viruses other than HIV and does not include anti-HIV drugs. Many antivirals are nucleoside analogues, although new classes of enzyme inhibitors are being developed for treatment of HIV (proteases) and enteroviruses. Antisense drugs and receptor blockers have recently been approved. Regardless of mechanism, antivirals are predominantly virustatic, not virucidal, and usually require help from the host immune system to either completely eliminate pathogens (e.g., influenza) or to provide sufficient immune surveillance to prevent a latent pathogen from reactivating (e.g., the herpesviruses). Viruses by nature are intracellular pathogens, using the host cell to produce progeny. Often the viral pathogen uses the host cell machinery or enzyme system to facilitate replication. At times the virus usurps nearly the entire intracellular system for replication and may shut down all functional host cell output for host-determined products. Because of the intracellular nature of viruses and because viruses use many "normal" host cell factors, functions, and systems for replication, antivirals can have notable toxicities to host cells. As antivirals inhibit viral activity in the viral-infected host cells (these encompass a minority of the total host cell numbers), they may also negatively affect functions in the virus-uninfected host cells. These alterations may be biochemical, detected only if sought specifically, or clinically obvious toxicities. Either may limit the use of some antivirals to severe or life-threatening situations.