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THE PHARMA REVIEW (JULY 2009)

Antiviral Chemotherapy

Dr. Ravinder Kaul

Abstract: The chemotherapy of bacterial infections has shown great progress in the present times. The search for chemical substances for antiviral therapy, on the contrary, could show initial gradual progress. Although the efforts in this research area are enormous, but still only few nucleoside analogues or so called antimetabolites have found their way in the therapy. This article presents the biology of viruses and the developments of nucleoside analogues and the mechanism of their action.

Introduction
The development of antiviral chemotherapy has progressed slowly compared to the development of antibacterial agents. Viruses, unlike bacteria, are totally dependent upon the cell they infest for much of the metabolic machinery required for their replication. Therefore, for an antiviral agent to be effective, it must be able to selectively inhibit virus replication without disrupting normal cellular functions. This selectively must be based on exploitable biochemical differences that exist between the processes involved in virus replication and those involved in replication of a normal cell. A number of virus specific sites which are amendable to antiviral intervention have been identified (e.g., adsorption, penetration, uncoating, synthesis of viral nucleic acids, synthesis of viral proteins, assembly, maturation and release). Of particular interest are the findings that the replication of many viruses involves enzymes specifically coded for by the virus (e.g., RNA polymerase, DNA polymerase, reverse transcriptase, nucleases, kinases, ribonucleotide reductase, methylases, guanyltransferase and proteases). These viral enzymes display characteristics that are quite distinct from their host cell counterparts and, therefore, are important targets for the design of selective antiviral agents.

It is impossible to deal here with all of the chemical entities which have shown antiviral activity. Therefore, this article will highlight only the pyrimidine and purin nucleoside analogues, primarily because the majority of the antiviral drugs that have been licensed for clinical use belong to the nucleoside analogues class of compounds. These compounds are primarily directed towards treating infections of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), certain infections of respiratory tract caused by respiratory syncytial virus (RSV) and acquired immunity deficiency syndrome called AIDS caused by human immunodeficiency virus (HIV).

Morphology of Virus
Viruses are not only smaller than cells; they also possess only one form of nucleic acid, either DNA or RNA (single or double stranded), never both forms together. The code capacity of such nucleic acid is sufficient only for a few genes. Viruses do not possess a cell structure, but are mainly a genome, a piece of hereditary information; chemically seen it is a piece of nucleic acid. This genome forms at the same time the so called infectious principle of the virus. In general nucleic acid of the virus are always covered by a protective protein coat, the so called capsid, the subunits are called capsomer. A capsid consists of multiple protein units for which only less code capacity is needed. Nucleic acid plus protein cover is called nucleocapsid. Some viruses possess in addition to their protein coat, an outer covering usually referred to as an outer envelope, which can contain lipids, protein and carbohydrates.

Many small viruses are built in form of icosahedrons, which has 20 triangular facets; spikes protruding from its outer surface help the virus recognise and attach to the cell (Fig. 1). The important DNA and RNA viruses and the infectious diseases caused by them are shown in Fig 2. It shows that the morphology can be very different in spite of essentially simple construction art.

 

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