ANTIVIRAL DRUGS

Viruses comprise a core genome of nucleic acid surrounded by a protein shell or capsid. Some viruses are further surrounded by a lipoprotein membrane or envelope. Viruses cannot replicate independently and, as such, are obligate intracellular parasites. The host’s pathways of energy generation, protein synthesis, and DNA or RNA replication provide the means of viral replication. Viral replication occurs in 5 sequential steps: host cell penetration, disassembly, control of host protein and nucleic acid synthesis such that viral components are made, 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 negatively impact normal pathways of the host. Antiviral drugs are characterized by a narrow therapeutic margin. Therapy is further complicated by viral latency, ie, the ability of the virus to incorporate its genome in the host genome, with clinical infection becoming evident without re-exposure to the organism. In vitro susceptibility testing must depend on cell cultures, which are expensive. More importantly, in vitro inhibitory tests do not necessarily correlate with therapeutic efficacy of antiviral drugs. Part of the discrepancy between in vitro and in vivo testing occurs because some drugs require activation (metabolism) to be effective.

Only a few agents have been found to be reasonably safe and effective against a limited number of viral diseases, and most of these have been developed in humans. Few have been studied in animals, and widespread clinical use of antiviral drugs is not common in veterinary medicine. Only a selection of the more promising agents and their purported attributes are briefly discussed.

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 therapy. Drugs that simply inhibit single steps in the viral replication cycle are virustatic and only temporarily halt viral replication. Thus, optimal activity of some drugs depends on an adequate host immune response. Some antiviral drugs may enhance the immune system of the host.

Several drug classes continue to be investigated mainly because of their in vitro antiviral activities. Their potential clinical usefulness remains obscure in most instances. Included among these agents are thiosemicarbazones, guanidine, benzimidazoles, arildone, phosphonoacetic acid, rifamycins and other antibiotics, and several natural products.

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