Introduction to Antiviral Drugs

The term virus has interesting meanings in popular culture: it is commonly used to describe some-thing that has or can spread quickly from person to person, such as a computer virus or a “viral” video,  a video that gains quick popularity through Inter-net or e-mail sharing. This usage represents a basic understanding of the high transmissibility of many respiratory viruses, such as influenza and the rhinoviruses that cause the common cold. However,  many less-understood viruses, particularly those that cause chronic disease, can be confusing.

The world of viruses is very different from that of prokaryotes and eukaryotes. Viruses are dependent on cells to replicate and cannot perpetuate without them. They are considerably smaller than eukaryotes and even much smaller than most prokaryotes, though they vary widely in size (see Figure 1). They are relatively simple organisms compared with prokaryotes or eukaryotes, but they outnumber all life forms on earth. Scientists have debated for many years about whether viruses are life forms or not, and no clear consensus yet exists.  The understanding of how they interact with and shape the existence of living cells, however, has increased greatly since they were described by Louis Pasteur in the late nineteenth century.

An in-depth discussion of the structure of viruses is beyond the scope of this text, but a basic understanding of viruses will help you understand the actions of antiviral drugs. Viruses are highly di-verse, though nearly all of them share a few com-mon characteristics. Many are covered by a viral envelope as their outmost layer, composed of elements of the host cell membrane, endoplasmic reticulum, or nuclear envelope. This layer covers the  capsid, a shell composed of identical building blocks of capsomeres. The capsid protects the viral nucleic acid, which is either DNA or RNA but not both (as in cells). The DNA or RNA can be either single- or double-stranded. Finally, many viruses contain enzymes that catalyze reactions that lead to their replication or cell entry. Viruses cannot synthesize their own components to replicate—they are dependent on host cellular processes for all synthetic functions. Individual complete particles of virus are termed virions.

The specific steps of the viral life cycle differ from virus to virus, but they follow the same basic pathway. Viruses spread from host to host through   various means, some through direct inhalation,  some through direct fluid exchange, some through vectors such as mosquitoes. Once a virus reaches its target cell, it has to penetrate the cell membrane. Specific receptors on the cell and viral sur-faces often facilitate this process. The virus then uncoats and releases its genetic information from the capsule into the host cell. The host cell reads the genetic material and begins to translate it into viral proteins. How exactly this proceeds depends on the form in which the genetic material exists in the virus. In some cases, the genetic material is en-coded as RNA. In the group of viruses known as retroviruses, the RNA genetic material is first translated into DNA (via an enzyme known as re-verse transcriptase) before integrating into the host genome. For these viruses or those viruses whose genome is already encoded as DNA, transcription into messenger RNA occurs, followed by translation into protein. Once the pieces of the puzzle are built, the viral enzymes assemble them into complete virions and they are finally released from the cell. The available antiviral drugs are aimed at various steps in this cycle. Some are aimed at spe-cific receptors against specific viruses (such as influenza), and some are aimed at more general steps to attack multiple viruses.

The pharmacotherapy of viral infections is different from that of bacterial infections. Patient-specific susceptibility results are rarely available,     leaving practitioners to choose therapies based upon general patterns of susceptibility for viral infections (HIV is a notable exception). While viruses can be cultured, many viral illnesses are diagnosed through genetic testing for viral antigens or nucleic acids. These tests can be followed quantitatively to see if an infection improves, but symptoms are usually followed instead. Most common viral infections have no effective pharmacotherapeutic remedy, which is a fancy way of saying that there is still “no cure for the common cold.”

References

Gallagher ,J.C. and MacDougall ,c. (2012). Antibiotics Simplified. Second Edition. Jones & Bartlett Learning, LLC.