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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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