Figure 4.

Illustration of the effect of anti-influenza drugs. The fitness landscape is replotted from figure 2, with arrows added to explain the functioning of different anti-influenza drugs. NA inhibitors reduce k₋, illustrated by the solid (strong reduction) and dashed (weak reduction) black arrows. Influenza can evolve resistance and regain fitness by mutating the NA protein, such that the drug does not bind well anymore. This leads to an effective restoration of NA function and increase in k₋. Another way to restore fitness is by mutating HA to reduce its binding activity (dotted black arrow). The solid and dashed white arrows illustrate hypothetical drugs that increase NA or decrease HA activity (see the text for explanation). (Online version in colour.)