Antiviral Agents

Abstract

Since the discovery of the first virus >100 years ago, thousands of different viruses have been identified and characterized, and a number of plant, animal, and human ailments have been traced to viral origin. The rapid advances made in tools and techniques of molecular biology in the last 40 years, coupled with cooperative efforts in genetics and biochemical fronts, have afforded intricate details of the structure, function, replication, and genomic makeup of a host of viruses. As there are too many viruses to give even short accounts, this article focuses on only those that have some relevance to human diseases. But, since the list of all human viruses would still be too long to give detailed descriptions for each, the focus is further narrowed down to four major viruses that are currently perceived to threaten global health. These four viruses include HIV (human immunodeficiency virus, which causes AIDS), HBV and HCV (hepatitis B and C viruses that cause liver damage), and the more recent WNV (West Nile virus that causes brain inflammation). Nevertheless, an attempt has been made to classify all the known major viruses based on their shape, size, symmetry, hosts, and chemical composition that includes nucleic acid, protein, and presence or absence of lipid envelope. As they are a form of life that cannot replicate outside a host cell, viruses have evolved to develop complex and diverse interactions with higher organisms. Therefore, it was long believed that the development of antiviral agents that would specifically disrupt the viral replication process without affecting the normal metabolic events of the host would be difficult. Thanks to excellent advances in virology, several targets that are unique to the viruses have now been identified and successfully explored. This article briefly describes the general processes of viral infection to point out potential targets for selective antiviral agents. These targets are then classified into two major virus‐specific processes, including ( a ) early events of viral adsorption, penetration and uncoating, and ( b ) later synthetic events that concern intracellular replication of the virus. While there are only limited choices of candidates dealing with the early events, a much larger pool of candidates exists for targeting the later events in a virus life cycle, and they are known to be virus‐specific. The viruses synthesize and utilize specific enzymes and proteins, and more importantly, the replication of viral genomes is also virus‐specific. Nucleoside analogues which target these later events of viral life cycles have played major roles as antiviral agents against almost all the major viruses, and therefore, a special emphasis has been placed on this class of compounds in this review article. Prophylactic measures such as vaccine immunization have also been discussed under each of the four major viruses mentioned.