Viral Exposure Therapy, Antiviral Drug Development

Viral Exposure Therapy, Antiviral Drug Development

█ BRIAN D. HOYLE

Several National Institute of Health and Defense Department funded programs are currently attempting to develop drugs that can be used to combat viruses most likely to be used by bioterrorists.

Antiviral drugs are compounds that are used to prevent or treat viral infections via the disruption of an infectious mechanism used by the virus, or to treat the symptoms of an infection. In addition to the development of vaccines, researchers are attempting to develop fast action identification and pharmacogenetic protocols for the development of effective anti-viral drugs that could potentially remediate some of the symptoms of viral exposure or early stage infection.

Different types of antiviral drugs have different modes of operation. One specific class of antiviral drugs are known as the antiretroviral drugs. These drugs target those viruses of clinical significance called retroviruses that use the mechanism of reverse transcription to manufacture the genetic material needed for their replication. The prime example of a retrovirus is the Human immunodeficiency virus (HIV), which is the viral agent of acquired immunodeficiency syndrome (AIDS). The development of antiviral drugs has been stimulated by the efforts to combat HIV.

Specific antiviral agents are designed to thwart the replication of whatever virus they are directed against. One means to achieve this is by blocking the virus from commandeering the host cell's nuclear replication machinery in order to have its genetic material replicated along with the host's genetic material. The virus is not killed directly. But the prevention of replication will prevent the numbers of viruses from increasing, giving the host's immune system time to deal with the stranded viruses.

The incorporation of the nucleotide building blocks into deoxyribonucleic acid (DNA) can be blocked using the drug idoxuridine or trifluridine. Both drugs replace the nucleoside thymidine, and its incorporation produces a nonfunctional DNA. However, the same thing happens to the host DNA. So, this antiviral drug is also an anti-host drug.

Blockage of the viral replicative pathway by mimicking nucleosides can also be successful. But, because the virus utilizes the host's genetic machinery, stopping the viral replication usually affects the host cell.

Another tack for antiviral drugs is to block a viral enzyme whose activity is crucial for replication of the viral genetic material. The drug is converted in the host cell to a compound that can out-compete another compound for the binding of the viral enzyme, DNA polymerase, which is responsible for building DNA. The incorporation of the drug into the viral DNA stops the formation of the DNA.

Other antiviral drugs are directed at the translation process, whereby the information from the viral genome that has been made into a template is read to produce the protein product. For example, the drug ribavirin—used to combat the 2003 global Severe Acute Respiratory Syndrome (SARS) pandemic—inhibits the formation of messenger ribonucleic acid.

Still other antiviral drugs are directed at earlier steps in the viral replication pathway (e.g., blocking penetration into the host cell or release of nuclear material).

Antiviral therapy also includes molecular approaches. The best example is the use of oligonucleotides. These are sequences of nucleotides that are specifically synthesized to be complimentary with a target sequence of viral ribonucleic acid. By binding to the viral RNA, the oligonucleotide blocks the RNA from being used as a template to manufacture protein.

The use of antiviral drugs is not without risk. Host cell damage and other adverse host reactions can occur. Thus, the use of antiviral drugs is routinely accompanied by close clinical observation.

█ FURTHER READING:

BOOKS:

Kurstak, Edouard, ed. Control of Virus Diseases. New York: Marcel Dekker, 1993.

ELECTRONIC:

Pan American Health Organization, World Health Organization. Severe Acute Respiratory Syndrome (SARS) <http://www.paho.org/English/HCP/HCT/EER/sars.htm> (April 6, 2003).

SEE ALSO

Bioshield Project
Bioterrorism, Protective Measures
Viral Biology