(Note: This article was written in 1996. Therefore, newer drugs may be available. Ed.)
The field of antiviral drugs is expanding rapidly, although progress has been slow for several reasons, which we will discuss. However, with the importance of exotic new human viruses, such as AIDS, Hantavirus, Ebola, and the like, the effort to develop effective drugs to combat these new threats has been intensified.
Very few commercially available antiviral drugs are on the market, even in human medicine. The first reason that antivirals have lagged behind the development of antibacterial drugs is that until recently medicine has been able to manufacture safe and effective vaccines. Actually, much research was conducted during the late 50’s and early 60’s in the area of antiviral drugs, but advances in immunology and vaccine research essentially nullified the need for antivirals.
During this period, Salk and Sabin developed an effective vaccine to the poliovirus. We also conquered smallpox and have virtually eradicated it from the earth. So, it appeared that we could create vaccines to protect us from dangerous viruses, at least in the western world.
The third-world nations still had viruses that were devastating, but western medicine deemed these unimportant and relegated them to academic pursuits. Many of these third-world viruses were not responsive to routine vaccine development or no funding was available to develop the vaccines. And, during that time period, world travel was limited compared to today such that the spread of an exotic viral disease could be minimized. Therefore, the advances made in the vaccine field, beneficial as they were, were among the many factors that contributed to the lag in development of antiviral drugs.
The next reason antiviral drugs lagged behind, as I alluded to earlier, is that no “significant” viruses threatened western society to any great extent. An abundance of extremely dangerous viruses exist in the third world, Rift Valley fever, Ebola, dengue, Philippine hemorrhagic fever, and the list goes on. But, here in the U.S. and in Europe, we either lacked the vectors, such as mosquitoes or other insects, that transmitted the viruses, or the number of cases were so low that they could be contained before they became problematic. Therefore, western medicine did not invest any funding or much interest, beyond academic, in these viral diseases. However, research into vaccine development was conducted with some of these diseases with mixed results by various countries and world health organizations.
Another reason antivirals were late in development is that the technology to dissect and understand the molecular biology of viruses had to be developed. The advent of DNA research has greatly advanced our understanding of viruses, and the field of molecular biology was mostly responsible for creating the picture we have today of viral biology.
It was not until the early and middle 1970s that western society was faced with its first really significant viral challenges. Remember how we all used to joke about genital Herpes and the embarrassment of contracting that disease? But by today’s standards, Herpes is the lesser of much greater evils. Herpesvirus was not life threatening to adults that contracted it, although it caused considerable mental and physical anguish. And, this was a disease that, like AIDS, had an unnecessary stigma attached to it.
However, this disease became widespread across all class strata, and as a result, the drug companies had an incentive to develop an antiviral agent to help combat Herpes. Vaccine researchers soon discovered that Herpesvirus is particularly unresponsive to most conventional vaccine approaches. This is because of the complex biology of the Herpes viruses, which is beyond the scope of this article. The Burroughs-Wellcome company marketed the first truly effective antiviral drug for Herpes, which was acyclovir under the trade name Zovirax™.
Hepatitis B is another human virus that was erupting at this time. This was and still is a devastating and dangerous virus. Until recently, no vaccine existed for this disease, and there are still no truly effective antiviral drugs for Hepatitis B.
The most important and most threatening virus in western culture is AIDS, Acquired Immuno-Deficiency Syndrome, caused by a retrovirus called HIV-1 or Human Immunodeficiency Virus #1. This virus is still eluding vaccine development. Many somewhat effective antiviral agents are in-use against this disease, and new ones are being developed almost daily. The hope is that this can be a controllable disease within the next few years if not a curable one for a while.
“What has all this got to do with bird medicine?” you may ask. Well, as veterinarians, we rely to a great extent on the human pharmaceutical sector to provide agents and biologics that we can alter or use for our patients. At this time, only one effective antiviral agent is used in avian patients. That drug is acyclovir. We use acyclovir in outbreaks of psittacine Herpes or Pacheco’s disease. The drug does not cure the disease, but limits clinical signs in those who are infected and prevents infection in naive birds.
Acyclovir drug is difficult to administer because it must be given orally about four times daily. The injectable form is caustic to the tissue, and birds can die just from the stress of the injections.
The drug has proven effective in the field and in clinical trials. Acylcovir works by forming a particular metabolite that inhibits DNA synthesis by the virus without harming cells. However, you are left with the uneasy thought that you may have saved your favorite Tres-Marie double-yellow-headed Amazon, but is the bird still shedding virus. This question is difficult to answer because we know that just as in human Herpes, the avian host is almost always infected for life although shedding is intermittent. So, you may save the collection but you don’t know if a time-bomb is planted in your aviary.
Several vaccines have been developed against Pacheco’s disease, which offer varying levels of protection. These varying levels of protection are because of the great variance in Herpes virus strains. Just as in our human influenza vaccines, we have to get a new Pacheco’s vaccine every year because the virus changes in some way.
Acyclovir is the only antiviral drug in use in avian medicine. Several drugs have been tried against PBFD (psittacine beak-and-feather disease) but to no avail. PBFD is a prime example of why it is difficult to combat viruses. The main reason we cannot develop antiviral drugs or mass produce the vaccine is that we cannot grow the virus in vitro, meaning to grow the virus in the test tube. So, we have to rely on a living bird to propagate the PBFD virus making very low amounts available to study the virus and develop antivirals and vaccines. If you cannot grow the virus to mass produce it, then progress will be slow and difficult.
Great strides have been made in the area of polyomavirus research, and a new vaccine has been marketed. Hopefully, it will be as efficacious in field use as the vaccine developers anticipate. However, no antiviral drugs are in use against polyoma.
We have not discussed a multitude of avian viral diseases and putative viral diseases. However, research is ongoing, although the researchers need your help.
This has been a cursory view of a complex and fascinating field. Antiviral drugs will continue to become more important and vital agents in medicine, and I am excited about the prospects for development of antivirals in avian medicine.
It is only through your efforts and support for valuable research, such as that conducted by Dr. David Phalen at Texas A&M University, that the field can advance. Dr. Phalen has done much to contribute to our understanding of avian polyomavirus and is currently working on other avian diseases that are possibly of viral origin such as PDS (proventricular dilation syndrome or macaw wasting disease) and papillomatosis. Researchers like Dr. Phalen are our greatest hope to illuminate and conquer these avian viral plagues.
(Dr. Phalen is no longer at TAMU. Ed.)
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