FIG. 5.
Model of the reaction pathway for the N-to-A transition. (A) Reaction pathway for the uncatalyzed (thermally mediated) conversion. The pathway proceeds through a single transition state, N†, whose Ea is independent of drug binding (25). (B) Reaction pathway for the receptor-mediated conversion. Binding of the receptor to N produces an initial virus receptor complex, NR. The receptor-mediated reaction goes through an intermediate, the activated virus receptor complex N∗R. R77975 and R78206 raise the Ea of the transition state for this step, N†R, such that it becomes rate limiting. The horizontal dashed line represents the energy barrier for the uncatalyzed reaction, which is 145 kcal/mol.