For many years the possibility of treating viral infections with drugs appeared remote because viruses enter host cells and make use of host cell enzymes and constituents to large extent. A drug that would block virus reproduction was also thought to be toxic for the host. Inhibitors of virus specific enzymes and life cycle processes have now been discovered, and several drugs are used therapeutically.
Most antiviral drugs disturb either critical stage in the virus life cycle or the synthesis of virus specific nucleic acid. Amantadine and rimantadine can be used to prevent influenza A infections. When given in time, it will reduce the incidence of influenza by 50 % to 70% in an exposed population. Amantadine blocks the penetration and uncoating of influenza virus particles.
Adenine arabinoside or vidarabine disrupts the activity of DNA polymerase and several other enzymes involved in DNA and RNA synthesis and function. It is given intravenously or applied as an ointment to treat herpes infection.
A third drug acyclovir is also used in the treatment of herpes infection. Upon phosphorylation, acyclovir resembles deoxy-GTP and inhibits the virus DNA polymerase. Unfortunately acyclovir resistant strains of herpes are already developing. Effective acyclovir derivatives and relatives are now available. Valacyclovir is an orally administered prodrug form of acyclovir. Ganciclovir, penciclovir, and its oral form famciclovir are effective in treatment of herpesviruses.
Another kind of drug, foscarnet inhibits the virus DNA polymerase in different way. Foscanet is an organic analogue of pyrophosphate that binds to the polymerase active site and blocks the cleavage of pyrophosphate from nucleoside triphosphate substrates. It is used in treating herpes and cytomegalo virus infection.
Several broad-spectrum anti-DNA virus drugs have been developed. A good example is the drug HPMC or cidofovir. It is effective against papovaviruses, adenoviruses, herpesviruses, iridoviruses and poxviruses. The drug acts on the viral DNA polymerase as a competitive inhibitor and alternative substrate of dCTP. It has been used primarily against cytomegalovirus but also against herpes simplex and human papiloma virus infections.
Research on anti HIV drugs has been particularly active. Many of the first drugs developed were reverse transcriptase inhibitors such as azidothymidine (AZT) or zidovudine, lamivudine (3TC), didanosine (DDI) zalcitabine and staviine. These interfere with reverse trancriptase activity and therefore block HIV reproduction. More recently HIV protease inhibitors have been developed. Three of the most important are saquinvir, indinavir, and ritovir. These mimic the peptide bound that is normally attacked by the protease. The most successful treatment regimes involve a cocktail of agents giving at high dosages to prevent the development of drug resistance. For example the combination of AZT, 3TC, and ritonavir is very effective in reducing HIV plasma concentrations almost to zero. However, the treatment does not seem able to eliminate latent proviral HIV DNA that still resides in memort T cells, and possibly elsewhere.
The most publicized antiviral agents are interferons. These small proteins produced by the host inhibit virus replication and may be clinically useful in the treatment of influenza, hepatitis, herpes and colds.
