18. ANTIVIRAL DRUGS

Viruses (from Latin: virus, poison) are exceedingly small intracellular pathogens unable to replicate outside cells (obligate parasites). They range in size from 20 to 300 nm in diameter (on average 100 times smaller than bacteria). Viruses have no systems for protein synthesis; therefore, they use relevant structures of the macroorganism (host) which they infect. Mature viral particles - virions - consist of genetic material (DNA or RNA) within a protective protein coat (capsid). Together with capsid proteins, nucleic acids enclosed in the capsid form the nucleocapsid. Some viruses are additionally coated with outer lipid membranes (supercap-sid), which represent modified membranes of the host organism cells (fig. 18.1). The proteins

embedded into the viral lipid membrane and capsid proteins are encoded by the viral genome and have antigenic properties. Besides, some viruses [herpes viruses, human immunodeficiency virus (HIV), etc.] contain enzymes required for their replication. Like all other foreign agents, viruses cause formation of antibodies that may be used for serological diagnostics of viral infections. Most viruses contain one type of nucleic acid; this allows classifying them as DNAor RNA-containing viruses.

Fig. 18.1. Stages of virion's development on the example of human immunodeficiency virus: 1 - attachment; 2 - penetration; 3 - deproteinization; 4 - integration into genome; 5 - transcription; 6 - assembly; 7 - exit from the cell; 8 - viral maturation inhibitors

DNA-containing viruses include herpes viruses, adenoviruses, papillomaviruses, hepatitis B, smallpox viruses. Many pathogenic human viruses that cause smallpox, rabies, poliomyelitis and meningitis, hepatitis A and C

are RNA-containing viruses. They also include causative agents of most acute respiratory infections, such as influenza virus, rhinovirus, parainfluenza virus, respiratory syncytial viruses and some others. Retroviruses are a type of RNA-containing viruses, which include HIV and T-cell leukemia. The process of viral reproduction starts with their absorption on cell surface (fig. 18.2). In order to attach themselves to cellular membranes, viruses use cellular membrane proteins as receptors (receptors for neurotransmitters, cytokines, hormones, ion channels). For example, human immunodeficiency viruses attach to the surface of T-cells, where CD4 protein is expressed, using it as a receptor, while rabies viruses target nicotinic receptors of skeletal muscles. Virus attachment to the cell membrane is achieved when specific proteins of the viral membrane or capsid proteins bind to relevant structures on the host organism cells. Thus, HIV membrane glycopro-tein gp120 selectively binds to CD4 protein, and chemokine receptors of T-cells and macro-phages, while attachment of influenza virus to epithelial cells of the respiratory tract is mediated by hemagglutinin.