The conventional approach to control viral diseases is to develop effective vaccines, but this is not always possible. The objective of antiviral therapy is to eradicate the virus, while minimally impacting the host, and to prevent further viral invasion. However, the method of replication of viruses makes them a greater challenge to treat than bacteria.
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 are thus 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 five sequential steps:
host cell entry
capsid disassembly (uncoating)
control of host protein and nucleic acid synthesis to make viral components
assembly of viral proteins
release of the virus
Drugs that target viral processes must penetrate host cells. Given that viruses often modulate cell division, drugs that negatively affect a virus are also likely to negatively affect normal pathways of the host. For this reason, antiviral drugs have a narrow therapeutic margin, compared with antimicrobial drugs. Nephrotoxicosis is emerging as an adverse reaction to antiviral drugs in human medicine.
Treatment is further complicated by viral latency, the ability of the virus to remain dormant within the host cell (ie, by incorporating its genome into the host genome); reactivation can then lead to clinical signs of infection in the animal even if it has not been reexposed to the virus.
In vitro susceptibility testing depends on cell cultures, which are expensive. More importantly, in vitro inhibitory tests do not necessarily correlate with therapeutic efficacy of antiviral drugs. The discrepancy between in vitro and in vivo testing is due, in part, to the fact that some drugs require activation (metabolism) to be effective.
Only a few antiviral drugs are reasonably safe and effective, against a limited number of viral diseases, and most of these have been developed for use in humans. Few have been studied in animals, and widespread clinical use of antiviral drugs is not common in veterinary medicine. The advent of human immunodeficiency virus (HIV) and the development of the cat as a model of HIV infection has somewhat increased the animal knowledge base.
There are notable concerns that the use of antiviral agents in veterinary medicine, particularly in food-producing animals, leads to the development of resistance to these medications in human pathogens. In 2006, the FDA prohibited the extralabel use of adamantanes and neuraminidase inhibitors in chickens, turkeys, and ducks because of concern about the potential emergence of resistant strains of influenza A, including H5N1 avian influenza virus, in the human population. Resistance to adamantane antivirals has been documented in influenza A strains in both humans and poultry, and some human strains have also demonstrated resistance to neuraminidase inhibitors. Although extralabel drug use (ELDU) is not prohibited in other species, these antivirals should be considered to be reserved classes of drugs to preserve their efficacy in the human population, and they should be used only in instances of documented infection and only when other agents or measures are considered inadequate for patient survival.
Most antiviral drugs interfere with viral nucleic acid synthesis or regulation. Such drugs generally are nucleic acid analogues 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 drug targets. Drugs that simply inhibit single steps in the viral replication cycle are virostatic, only temporarily halting 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. Dosages of Antiviral Drugs lists the dosage rates for some commonly used antiviral drugs.
