Antiviral Drugs


First, remember (or review) the structure and function of a virus. Once attached to its specific target cell, it injects its DNA (or RNA) into the host cell. Once inside the 'infected' cell, this viral DNA (or RNA) replicates itself as well as using the existing machinery within the 'infected' cell to make more viral proteins. It then assembles itself and can now leave this cell to infect other cells.

Second, remember (or review) the structure and workings of DNA (or RNA). All the DNA strand consists of are 5-carbon deoxyribose (or ribose) sugars linked together by phosphate groups. Additionally, each 5-carbon sugar has one of four possible bases attached: A, G, C, or T. So in order to elongate a strand of DNA (or RNA), the cell simply links the 'sugar-base-phosphate' unit onto the existing 'sugar-base-phosphate' units already linked together forming the strand of DNA. We oversimplify this by saying that the DNA strand grows by adding additional bases. For example, our simplified explanation says that the DNA strand grows by adding an "A", or "G", or "C", or "T" base, one at a time. Remember that this "A", or "G" or "C" or "T" is the 'sugar-base-phosphate' unit with the base being either A, G, C, or T.

Thirdly, this is an oversimplified but essentially accurate explanation of how several antiviral drugs work. The antiviral drug will be incorporated into the growing DNA (or RNA) strand as if it were another 'sugar-base-phosphate' unit. Once this drug is incorporated into the growing DNA strand, no other 'sugar-base-phosphate' units can be attached, and so any further grows stops. Hence, terminating the growth of viral DNA within the infected cell.

As an example, let's discuss acyclovir as an antiviral drug for herpes simplex infection. Acyclovir is an analog of 2-deoxyguanosine ("G"). The acyclovir is in fact modified by enzymes made only by the virus so that the acyclovir can now be incorporated into the growing viral DNA strand instead of the "G". Once incorporated, any further elongation stops because unlike "G" that should be there, the acyclovir cannot attach any further nucleoties (acyclovir cannot attach any further "A"'s, or "G"'s, or "C"'s, or "T"'s).

A herpes simplex virus attaches to a susceptible host cell (seen on the right), fusing its envelope with the cell membrane, and releasing naked capsids that deliver viral DNA into the nucleus of the host cell, where it initiates the synthesis of viral DNA.

Acyclovir molecules entering the cell are converted to acyclovir monophosphate by virus induced thymidine kinase enzyme.
Host-cell enzymes add two more phosphates to form acyclovir triphosphate, which is transported to the nucleus.
Shown in red is the cleavage of phosphate from the acyclovir triphosphate by the herpes simplex's own enzymes, the herpes simplex's DNA polymerase enzyme incorporates the acyclovir monophosphate into the growing DNA strand as if it were 2-deoxyguanosine monophosphate (a "G" base).

Further elongation of the chain is impossible because acyclovir monophosphate lacks the attachment point necessary for the insertion of any additional nucleotides.

I. The acyclovir (as do other antiviral drugs) is mistakenly incorportated into the growing DNA strand. The enzymes adding in "A"'s, or "G"'s, or "C"'s, or "T"'s recognize acyclovir as a "G" and add it in.

II. The acyclovir does not have the proper structure to add any additional "A"'s, or "G"'s, or "C"'s, or "T"'s to it, and so the DNA strand cannot continue to elongate or grow. Once the acyclovir is incorporated, any further growth of viral DNA is terminated.

III. If I swallow my acyclovir drugs, isn't acyclovir going into all of my cells, and blocking the growth (or replication) of all my cell's DNA, not just the cells infected with virus? Not necessarily. As you read, the conversion of the original acyclovir into the form that is incorporated into the DNA is carried out by the virus's own enzyme. Therefore, only those cells that are infected with the virus will have this specific enzyme and convert the original acyclovir into the acyclovir that can be incorporated as a "G" base. Also, only the cells infected with virus have the enzyme that mistakenly recognizes acyclovir as a "G" base and puts it into the growing DNA strand. So, again, all of your non-virally infected cells will not that this viral enzyme and so not put acyclovir into growing DNA.


Anti-Influenza (A and B) Drugs


As new viruses emerge from the host cell, they are coated in a layer of glycolipid originating from the cell membrane. Haemagglutinin receptors from the virus are bound to these glycolipids. Neuraminidase cleaves the glycolipid from the haemagglutinin thus releasing the virus completely from the host cell.

The surfaces of influenza viruses are dotted with neuraminidase proteins. Neuraminidase, an enzyme, breaks the bonds that hold new virus particles to the outside of an infected cell. Once the enzyme breaks these bonds, this sets free new viruses that can infect other cells and spread infection. Neuraminidase inhibitors block the enzyme's activity and prevent new virus particles from being released, thereby limiting the spread of infection.