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Chemotherapy of Viral Infections

Viruses essentially consist of genetic material (nucleic acids, green strands in (A) and a capsular envelope made up of proteins (blue hexagons), often with a coat (gray ring) of a phospholipid (PL) bilayer with embedded proteins (small blue bars). They lack a metabolic system but depend on the infected cell for their growth and replication. Targeted therapeutic suppression of viral replication requires selective inhibition of those metabolic processes that specifically serve viral replication in infected cells. To date, this can be achieved only to a limited extent.

Viral replication as exemplified by Herpes simplex viruses (A): (1) The viral particle attaches to the host cell membrane (adsorption) by linking its capsular glycoproteins to specific structures of the cell membrane. (2) The viral coat fuses with the plasmalemma of the host cell and the nucleocapsid (nucleic acid plus capsule) enters the cell interior (penetration). (3) The capsule opens ("uncoating") near the nuclear pores and viral DNA moves into the cell nucleus. The genetic material of the virus can now direct the cell's metabolic system. (4a) Nucleic acid synthesis: The genetic material (DNA in this instance) is replicated and RNA is produced for the purpose of protein synthesis. (4b) The proteins are used as "viral enzymes" catalyzing viral multiplication (e.g., DNA polymerase and thymidine kinase), as capsomers, or as coat components, or are incorporated into the host cell membrane. (5) Individual components are assembled into new virus particles (maturation). (6) Release of daughter viruses results in spread of virus inside and outside the organism. With herpes viruses, replication entails host cell destruction and development of disease symptoms.

Antiviral mechanisms (A). The organism can disrupt viral replication with the aid of cytotoxic T-lymphocytes that recognize and destroy virus-producing cells (viral surface proteins) or by means of antibodies that bind to and inactivate extracellular virus particles. Vaccinations are designed to activate

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