Inhibitors of virus replication: recent developments and prospects

Julia Magden, Leevi Kääriäinen, Tero Ahola

The search for inhibitors of viral replication is dependent on understanding the events taking place at the molecular level during viral infection. All the essential steps during the viral life cycle are potential targets for antiviral drugs. Classical inhibitors of herpesvirus replication cause chain termination during viral DNA replication. Similarly, the HIV reverse transcriptase is the major target of anti-HIV compounds. The broad-spectrum antiviral agent ribavirin affects viral nucleic acid replication by multiple mechanisms. Another major enzyme encoded by many viruses is a protease responsible for the processing of virus-encoded polyproteins. The HIV protease has been very successfully targeted, and hepatitis C virus and rhinovirus protease inhibitors are being actively developed. The complex series of interactions during virus entry is a rapidly emerging and promising target for inhibitors of HIV and many other viruses. New anti-influenza drugs inhibit virus release from infected cells. Several stages of the viral life cycle remain incompletely characterized and are therefore poorly exploited in antiviral strategies. These include, among others, the RNA capping reactions catalyzed by many viruses, as well as the membrane association of replication complexes which is common to all positive-strand RNA viruses.