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Viruses are obligate intracellular parasites. That is, unlike bacteria, viruses depend on living host cells to replicate and function. Since viruses rely on the synthetic machinery of host cells, viruses can be extremely small. In many cases, the entire viral particle, or virion, consists only of nucleic acids (deoxyribonucleic acid [DNA] or ribonucleic acid [RNA]) surrounded by a protein shell, or capsid. Some viruses have an additional glycoprotein coat called an envelope.

Viral infections range from common minor illnesses, such as the common cold and cold sores, to life-threatening diseases, such as AIDS, Ebola, and severe acute respiratory syndrome (SARS). In addition, some viruses can cause certain types of cancer. For example, human papillomavirus is the primary causative agent of cervical cancer.

Viral transmission can occur in many ways. The most common ways that virions enter the body are via inhaled droplets (e.g., rhinovirus, the causative agent of the common cold), contaminated food or water (e.g., hepatitis A), direct contact from infected hosts (e.g., HIV), or direct inoculation by bites of infected vectors (e.g., dengue fever, transmitted by mosquitoes).

Viruses are complicated chemotherapy targets for several reasons. Since viruses rely on host cells’ machinery to function, the selective pharmacologic destruction of a virus without destroying human cells is difficult. Early treatment is critical, but frequently not possible because viral replication often peaks before clinical symptoms develop. Many antiviral agents also rely on a normal immune system to destroy the virus. Thus, immune suppression often lengthens viral illnesses. Finally, mutations that cause changes in viral structure and enzymes often lead to the emergence of drug-resistant viral strains. Some viruses (influenza A and B, hepatitis B virus [HBV]) can be effectively controlled by vaccines (see section Vaccines and Immune Globulins: Active and Passive Immunizations below).

Antiviral drugs can potentially exert their actions at several stages of viral replication, including (1) viral attachment and entry into the host cell; (2) uncoating of viral nucleic acid; (3) synthesis of early viral regulatory proteins; (4) synthesis of RNA or DNA nucleic acids; (5) late protein synthesis and processing; (6) viral packaging and assembly, and (7) virion release (Figure 28–1).

Figure 28–1.

The major sites of drug action on viral replication. Diseases in parentheses, see text.

One of the most important trends in viral chemotherapy, especially in the management of HIV infection, has been the introduction of combination drug therapy, in which more than one stage of viral replication is inhibited. The benefits of combination antiviral therapy include greater clinical effectiveness and the prevention or delay of drug resistance.

The antiviral agents covered in this chapter include drugs against herpes, HIV, influenza, HBV, and hepatitis C (HCV) (Figure 28–2).

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