Pause for thought

The effective treatment of viral diseases is fraught with problems. Viruses multiply rapidly so by the time the disease is identified the number of viruses in the body is huge and viruses regularly mutate so may develop ways of combating antiviral drugs. It is much more effective to prevent viral infections from breaking out in the first place through active immunisation programmes and by taking preventative methods (e.g. the use of condoms to prevent HIV transmission) to stop the spread of the disease.

The two main ways in which current antiviral medications work is either by altering genetic material within the host cell, which prevents the virus from multiplying, or by blocking the active site on enzymes within the host cell, which prevents the virus from leaving the cell. A good example for the first method is the use of acyclovir and ganciclovir against herpes infections. These have structures similar to deoxyguanosine so they ‘trick’ the viral enzymes into using it as a building block for the viral DNA.

Other antiviral medications that work by altering genetic material in the host cell are amantadine and rimantadine used in the past to treat influenza and the common cold. They are now almost 100% ineffective as viruses have developed resistance to them.

The syllabus lists oseltamivir (Tamiflu) and zanamivir (Relenza), used to treat influenza, as examples of antiviral medications that work by blocking the active site of enzymes. A comparison of their structures shows that oseltamivir is an ester and is less polar than zanamivir, which contains a carboxyl group, several hydroxyl groups and more amine groups than oseltamivir. In fact oseltamivir itself is inactive. It is a good example of a drug to use to explain the concept of ‘active metabolite’ as once it gets to the liver it is metabolized to its active form, oseltamivir carboxylate. Students can see that this is an example of ester hydrolysis as the ester group on the oseltamivir is hydrolysed to the carboxyl group with the release of methanol. These drugs work by acting as competitive inhibitors on the neuraminidase enzymes, which prevent the viruses from escaping from the host cell. It is worth pointing out that there is considerable controversy about the use and effectiveness of these two drugs, particularly oseltamivir. It is another example of where the profits of the pharmaceutical companies compete with the impartial gathering and reporting of clinical data.