Antiviral Drugs

The conventional approach to the control of viral diseases is to develop effective vaccines, but this is not always possible. The objective of antiviral activity is to eradicate the virus while minimally impacting the host and to prevent further viral invasion. However, because of their method of replication, viruses present a greater therapeutic challenge than do bacteria.

Viruses are made of a core of nucleic acid (DNA or RNA) surrounded by a protein shell or capsid. Some viruses are further surrounded by a lipoprotein membrane or envelope. Viruses cannot reproduce independently but depend on taking over the host cell’s machinery to perform that task. Viral replication occurs in 5 steps: host cell penetration, disassembly, control of host protein and nucleic acid synthesis to produce new viral proteins, assembly of viral proteins, and release of the virus.

Drugs that target viral processes must penetrate host cells; in doing so, they are likely to disrupt normal cellular activities. Antiviral drugs are characterized by a narrow therapeutic margin, meaning that the difference between a dose that is effective and one that causes adverse effects is often small. Treatment is further complicated by viral latency, which is the ability of the virus to incorporate its genome into the host genome. The virus can remain inactive for a long time, then begin reproducing and cause illness again. In vitro susceptibility testing, which is used to tell what drugs a particular virus can be treated with, must depend on cell cultures, and these tests are expensive. More importantly, these laboratory tests do not necessarily predict which antiviral drugs will work in the animal.

Most antiviral drugs interfere with viral nucleic acid synthesis or regulation. Such drugs generally are nucleic acid analogs that interfere with RNA and DNA production. Other mechanisms of action include interference with viral cell binding or interruption of virus uncoating. Some viruses contain unique metabolic pathways that serve as a target of drug treatment. Drugs that simply inhibit single steps in the viral replication cycle are called virustatic and only temporarily halt viral replication. Thus, optimal activity of some drugs depends on an adequate host immune response. Some antiviral drugs are designed to enhance the immune system of the host.