There are two important transition states shown in this mechanism, the first for the actual cleavage of the C-O bond leading to loss of the ROH fragment and the second for the formation of a new C-OH bond.
In the first transition state, notice how the enzyme assists the ionization of a water molecule, the transfer of its proton to the leaving OR group, and stabilizes the transient positive charge on the ring oxygen.
With knowledge of how the enzyme functioned, von Itzstein decided that a compound that looked like the carbohydrate in that key first transition state would be a good candidate for an anti-influenza drug that would function by preventing the release of viral particles from infected cells. Click here to go to the next stage in the story - synthesizing and testing a new compound.