Neuraminidase Inhibitors




The development of highly effective neuraminidase inhibitors became feasible when analysis of the three-dimensional structure of influenza neuraminidase revealed the location and structure of the catalytic site (see above).


Two successful agents zanamavir (delivered intranasally) and oseltamivir (delivered orally) have become important in influenza treatment and prophylaxis.


Both bind strongly to the enzyme active site and prevent release of progeny virions, thereby preventing infection of new cells and the further spread of infection.


When used within 24 to 30 hours of the onset of symptoms, either drug can shorten the duration of symptoms by one to three days, and these are also useful as prophylactic treatment.


In contrast to the adamantanes, zanamavir and oseltamivir cause very little toxicity and are associated with less problems of drug resistance. Each has a broad spectrum of action across influenza strains of both type A and type B, and a low rate of drug resistance makes each an important component in planning for future pandemics.


Stockpiles of drugs are maintained to provide rapid prophylaxis and treatment, if required in the lead-up period before a specific vaccine against a new pandemic strain becomes available.


However, cost and logistics will of course limit how extensively and for how long such treatment can be sustained in the face of a new pandemic.


More recently developed neuraminidase inhibitors include peramivir, an intravenous agent authorized for emergency use in hospitalized patients suffering from 2009 H1N1 influenza, and laninamivir, which is active against oseltamivir-resistant viruses and has such a long-lasting effect that a single inhalation on the first day of treatment appears to be effective.