Fighting the flu with Oseltamivir

Transition state analogues are molecules that closely resemble a subtrate’s transition state structure in a reaction catalyzed by enzymes. The study of transition state analogues is one of the few techniques of rational drug design used to develop new pharmaceuticals. One of the more well known drugs discovered through this technique is Oseltamivir, which is a potent therapy against the infectious influenza virus.

Oseltamivir is a competitive inhibitor for the enzyme neuraminidase and prevents neuraminidase from acting on its intended substrate, sialic acid. Neuraminidase is normally found on the influenza virus protein coat and hydrolyzes sialic acid molecules found on the exterior of host cell membranes to allow newly made viral particles to exit the original host cell, and begin infecting other host cells. Through the tight binding of Oseltamivir to neuraminidase’s active site, this process is inhibited, and the infectivity of the influenza virus is reduced. Due to the fact that Oseltamivir is a transition state analogue of sialic acid, their chemical structures are quite similar, as shown below: